Photodynamic therapy(PDT)can take place in the presence of three elements:Light with an appropriate wavelength;a photosensitizer;and the presence of oxygen.This type of treatment is very effective overall against bact...Photodynamic therapy(PDT)can take place in the presence of three elements:Light with an appropriate wavelength;a photosensitizer;and the presence of oxygen.This type of treatment is very effective overall against bacterial,viral and mycotic cells.In the last 10 years many papers have been published on PDT with different types of photosensitizers(e.g.,methylene blue,toluidine blue,indocyanine green,curcumin-based photosensitizers),different wavelengths(e.g.,460 nm,630 nm,660 nm,810 nm)and various parameters(e.g.,power of the light,time of illumination,number of sessions).In the scientific literature all types of PDT seem very effective,even if it is difficult to find a standard protocol for each oral pathology.PDT could be an interesting way to treat some dangerous oral infections refractory to common pharmacological therapies,such as candidiasis from multidrug-resistant Candida spp.展开更多
The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy.Here,we report two perylene diimide-based metallac...The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy.Here,we report two perylene diimide-based metallacages that can form stable host–guest complexes with planar conjugated molecules including polycyclic aromatic hydrocarbons and photosensitizers(hypocrellin A).Such host–guest complexation not only prevents the aggregation of photosensitizers in aqueous environments,but also offers fluorescence resonance energy transfer(FRET)from the metallacage to the photosensitizers to further improve the singlet oxygen generation(Φ_(Δ)=0.66).The complexes are further assembled with amphiphilic polymers,forming nanoparticles with improved stability for anticancer study.Both in vitro and in vivo studies indicate that the nanoparticles display excellent anticancer activities upon light irradiation,showing great potential for cancer photodynamic therapy.This study provides a straightforward and effective approach for enhancing the photosensitivity of conventional photosensitizers via host–guest complexation-based FRET,which will open a new avenue for host–guest chemistry-based supramolecular theranostics.展开更多
Aggregate-level photodynamic therapy(PDT)has attracted significant interest and driven substantial advances in multifunction phototheranostic platforms.As exem-plified by two typical instances of aggregation-caused quen...Aggregate-level photodynamic therapy(PDT)has attracted significant interest and driven substantial advances in multifunction phototheranostic platforms.As exem-plified by two typical instances of aggregation-caused quenching of reactive oxygen species(ROS)and aggregation-induced generation of ROS,the aggregation effect plays a significant role on the ROS generation of photosensitizers(PSs),which is worthy of in-depth exploration and full utilization.However,in contrast to the well-developed researches on the aggregation effect on luminescence,the studies concerning the aggregation effect on ROS generation are currently in a relatively nascent and disjointed stage,lacking guidance from afirmly established research paradigm.To advance this regard,this review aims at providing a consolidated overview of the fundamental principles and research status of aggregation effects on the ROS generation.Here,the research status can be organized into two main facets.One involves the comparison between isolated state and aggregated state,which is mainly conducted by two methods of changing solvent environments and adding adjuvants into a given solvent.The other underscores the distinctions between different aggregate states,consisting of three parts,namely comparison within the same or between different categories based on the classification of single-component and multicomponent aggregates.In this endeavor,we will present our views on cur-rent research methodologies that explore how aggregation affects ROS generation and highlight the design strategies to leverage the aggregation effect to optimize PS regiments.We aspire this review to propel the advancement of phototheranostic plat-forms and accelerate the clinical implementation of precision medicine,and inspire more contributions to aggregate-level photophysics and photochemistry,pushing the aggregate science and materials forward.展开更多
Currently three major problems seriously limit the practical application of can-cer photodynamic therapy(PDT):(i)the hypoxic tumor microenvironment(TME);(ii)low generation efficiency of toxic reactive oxygen species(RO...Currently three major problems seriously limit the practical application of can-cer photodynamic therapy(PDT):(i)the hypoxic tumor microenvironment(TME);(ii)low generation efficiency of toxic reactive oxygen species(ROS)in aggre-gates and(iii)shallow tissue penetration depth of excitation light.Very limited approaches are available for addressing all the above three problems with a single design.Herein,a rational“three birds with one stone”molecular and nanoengi-neering strategy is demonstrated:a photodynamic nanoplatform U-Ir@PAA-ABS based on the covalent combination of lanthanide-doped upconversion nanoparti-cles(UCNPs)and an AIE-active dinuclear Ir(III)complex provides a low oxygen concentration-dependent type-I photochemical process upon 980 nm irradiation by Föster resonance energy transfer(FRET).U-Ir@PAA-ABS targets mitochondria and has excellent phototoxicity even in severe hypoxia environments upon 980 nm irradiation,inducing a dual-mode cell death mechanism by apoptosis and ferropto-sis.Taken together,the in vitro and in vivo results demonstrate a successful strategy for improving the efficacy of PDT against hypoxic tumors.展开更多
Photodynamic therapy(PDT)is a promising cancer treatment.This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]−10,15,20-tr...Photodynamic therapy(PDT)is a promising cancer treatment.This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]−10,15,20-triphenyl-porphyrin(DTP)mediated PDT(DTP-PDT).Cell viability,reactive oxygen species(ROS),and apoptosis were measured with a Cell Counting Kit-8 assay,DCFH-DA fluorescent probe,and Hoechst staining,respectively.Cell apoptosis-and autophagy-related proteins were examined using western blotting.RNA sequencing was used to screen differentially expressed mRNAs(DERs),and bioinformatic analysis was performed to identify the major biological events after DTP-PDT.Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells.The ROS scavenger N-acetyl-L-cysteine(NAC)and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity.DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2,which could also be inhibited by NAC or SB203580.The level of LC3B-Ⅱ,a marker of autophagy,was increased by DTP-PDT.A total of 3496 DERs were obtained after DTP-PDT.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes,the nuclear lumen,protein binding,cell cycle,protein targeting to the endoplasmic reticulum,and ribosomal DNA replication.Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints.Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes.Therefore,DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy,partly through ROS and the P38 MAPK signaling pathway.Genes associated with the cell cycle,ribosomes,DNA replication,and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.展开更多
Current antitumor monotherapy has many limitations,highlighting the need for novel synergistic anticancer strategies.Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory rol...Current antitumor monotherapy has many limitations,highlighting the need for novel synergistic anticancer strategies.Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory role in tumorigenesis and treatment.Photodynamic therapy(PDT)causes irreversible chemical damage to target lesions and is widely used in antitumor therapy.However,PDT’s effectiveness is usually hindered by several obstacles,such as hypoxia,excess glutathione(GSH),and tumor resistance.Ferroptosis improves the anticancer efficacy of PDT by increasing oxygen and reactive oxygen species(ROS)or reducing GSH levels,and PDT also enhances ferroptosis induction due to the ROS effect in the tumor microenvironment(TME).Strategies based on nanoparticles(NPs)can subtly exploit the potential synergy of ferroptosis and PDT.This review explores recent advances and current challenges in the landscape of the underlyingmechanisms regulating ferroptosis and PDT,as well as nano delivery system-mediated synergistic anticancer activity.These include polymers,biomimetic materials,metal organic frameworks(MOFs),inorganics,and carrier-free NPs.Finally,we highlight future perspectives of this novel emerging paradigm in targeted cancer therapies.展开更多
Photodynamic therapy(PDT)is applied as a robust therapeutic option for tumor,which exhibits some advantages of unique selectivity and irreversible damage to tumor cells.Among which,photosensitizer(PS),appropriate lase...Photodynamic therapy(PDT)is applied as a robust therapeutic option for tumor,which exhibits some advantages of unique selectivity and irreversible damage to tumor cells.Among which,photosensitizer(PS),appropriate laser irradiation and oxygen(O_(2))are three essential components for PDT,but the hypoxic tumor microenvironment(TME)restricts the O_(2) supply in tumor tissues.Even worse,tumor metastasis and drug resistance frequently happen under hypoxic condition,which further deteriorate the antitumor effect of PDT.To enhance the PDT efficiency,critical attention has been received by relieving tumor hypoxia,and innovative strategies on this topic continue to emerge.Traditionally,the O_(2) supplement strategy is considered as a direct and effective strategy to relieve TME,whereas it is confronted with great challenges for continuous O_(2) supply.Recently,O_(2)-independent PDT provides a brand new strategy to enhance the antitumor efficiency,which can avoid the influence of TME.In addition,PDT can synergize with other antitumor strategies,such as chemotherapy,immunotherapy,photothermal therapy(PTT)and starvation therapy,to remedy the inadequate PDT effect under hypoxia conditions.In this paper,we summarized the latest progresses in the development of innovative strategies to improve PDT efficacy against hypoxic tumor,which were classified into O_(2)-dependent PDT,O_(2)-independent PDT and synergistic therapy.Furthermore,the advantages and deficiencies of various strategies were also discussed to envisage the prospects and challenges in future study.展开更多
Background:((1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin methylpyridin-1-ium iodide salt(TBZPy)is a novel photosensitizer that displays excellent photodynamic properties.However,There are f...Background:((1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin methylpyridin-1-ium iodide salt(TBZPy)is a novel photosensitizer that displays excellent photodynamic properties.However,There are few reports on the mechanism of action of the TBZPy photodynamic.Previous studies revealed that photodynamic therapy(PDT)could induce endoplasmic reticulum stress by acting on the endoplasmic reticulum.Therefore,in this study,we investigated the effects of endoplasmic reticulum stress induced by TBZPy-PDT in treating High-risk human papillomavirus(HR-HPV)infection and their underlying mechanisms.Methods:The human cervical cancer cell line HeLa(containing whole genome of HR-HPV18)was treated with TBZPy-PDT.Cell migration,invasion,and colony-forming ability were evaluated using wound-healing,Transwell invasion,and colonyforming assays,respectively.Through western blot analysis,we determined the level of expression of the PI3K/AKT and PERK/eIF2αpathway proteins and the proteins associated with calcium trafficking and apoptosis.The calcium levels in the cytoplasm were detected via flow cytometry.Results:The result shows that TBZPy-PDT could inhibite the migration,invasion,and colony forming ability of infected HeLa cells by downregulating the PI3K/AKT pathway in vitro.And we found that TBZPy-PDT induced endoplasmic reticulum stress-specific apoptosis via the PERK/eIF2αpathway.Moreover,TBZPy-PDT increased the levels of calcium and calmodulin,while decreasing the levels of endoplasmic reticulum calcium-binding proteins.Conclusions:TBZPy-PDT is effective on treating human papillomavirus-infected cells.Targeting the PI3K/AKT and PERK/eIF2αpathways and the endoplasmic reticulum stress process may help improve the effects of TBZPy-PDT for treating high-risk human papillomavirus infection.展开更多
Port-wine stain(PWS)is a congenital capillary malformation that occurs in 0.3%–0.5%of newborns.The pulsed dye laser is the current gold standard treatment for PWS;however,its efficacy is poor.Photosensitizer photodyn...Port-wine stain(PWS)is a congenital capillary malformation that occurs in 0.3%–0.5%of newborns.The pulsed dye laser is the current gold standard treatment for PWS;however,its efficacy is poor.Photosensitizer photodynamic therapy(PDT)is considered a promising treatment for PWS.Here we provide a comprehensive overview of PDT.展开更多
Objective： To evaluate the clinical effectiveness and adverse effects of photodynamic therapy （PDT） for the upper gastrointestinal tract cancers. Methods： 56 patients with upper gastrointestinal cancers in differe...Objective： To evaluate the clinical effectiveness and adverse effects of photodynamic therapy （PDT） for the upper gastrointestinal tract cancers. Methods： 56 patients with upper gastrointestinal cancers in different clinical stages were treated with PDT. Diode laser （630 nm） was used as the light source and the parameters were as follows： power density 200 to 400 mW/cm, energy density 100 to 300 J/cm. PHOTOFRIN was used as photosensitizer, which was given in a dose of 2 mg/kg intravenously 12-24 h before irradiation. Results： Evaluation of the 56 patients＇ therapeutic effectiveness showed that 6 patients （10.7%） had a complete response （CR）, 33 patients （58.9%） partial response （PR）, 12 patients （21.4%） mild response （MR）, and 5 patients （8.9%） no response （NR）. The total response rate （CR＋PR） was 69.6%. No patients had severe adverse effects in this group. Conclusion： PDT is an effective and safe palliative modality for upper gastrointestinal tract cancers.展开更多
AIM:To compare the efficacy of low-fluence photodynamic therapy(PDT) combinations in the treatment of age-related macular degeneration(AMD).· METHODS:Forty-five previously untreated eyes of 45 patients with exuda...AIM:To compare the efficacy of low-fluence photodynamic therapy(PDT) combinations in the treatment of age-related macular degeneration(AMD).· METHODS:Forty-five previously untreated eyes of 45 patients with exudative AMD whose best-corrected visual acuity(BCVA) was ≥0.3(Snellen) were enrolled.15 patients in Group I underwent low-fluence PDT(25J/cm2-300mW/cm2-83sec) and intravitreal pegaptanib combination,15 patients in Group II underwent PDT(50J/cm2-600mW/cm2-83sec) and intravitreal pegaptanib combination while,15 patients in Group III underwent intravitreal pegaptanib monotherapy.Complete ophthalmologic examinations were performed in pre and post treatment visits,and the results were statistically analised.A clinical activity score(CAS) was calculated by using changes in lesion size,amount of hemorrhage,staining pattern in FA and OCT measurement of intra/subretinal fluid.≤3 logMAR lines of decrease in BCVA and decrease in CAS were considered as successful treatment.· RESULTS:The mean age of 19 female(42.2%) and 26 male(57.8%) patients was(72.82±8.02) years.Mean follow-up was(13.93±5.87) months.Lesion type was occult in 28 eyes(62.2%).Treatment success rates according to BCVA assessments were 86.7%,80%,60% and mean BCVA decrease were 0.3,1.0,2.2 logMAR lines in Group I,II and III,respectively(P >0.05).According to the changes in central macular thickness and CAS,no difference was found among the study groups(P =0.850 and P =0.811,respectively).Patients treated with combination regimens had lower intravitreal injection frequencies(P =0.015).· CONCLUSION:Combination regimen with intravitreal pegaptanib and low-fluence PDT seems to be safe and effective in stabilizing the clinical activity and BCVA in exudative AMD.·展开更多
To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma.METHODSIncluded studies compared outcomes with photodynamic therapy and biliary ...To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma.METHODSIncluded studies compared outcomes with photodynamic therapy and biliary stenting (PDT group) vs biliary stenting only (BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubMed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I<sup>2</sup> statistic.RESULTSTen studies (n = 402) that met inclusion criteria were included in this analysis. The P for χ<sup>2</sup> heterogeneity for all the pooled accuracy estimates was > 0.10. Pooled odds ratio for successful biliary drainage (decrease in bilirubin level > 50% within 7days after stenting) in PDT vs BS group was 4.39 (95%CI: 2.35-8.19). Survival period in PDT and BS groups were 413.04 d (95%CI: 349.54-476.54) and 183.41 (95%CI: 136.81-230.02) respectively. The change in Karnofsky performance scores after intervention in PDT and BS groups were +6.99 (95%CI: 4.15-9.82) and -3.93 (95%CI: -8.63-0.77) respectively. Odds ratio for post-intervention cholangitis in PDT vs BS group was 0.57 (95%CI: 0.35-0.94). In PDT group, 10.51% (95%CI: 6.94-14.72) had photosensitivity reactions that were self-limiting. Subgroup analysis of prospective studies showed similar results, except the incidence of cholangitis was comparable in both groups.CONCLUSIONIn palliation of unresectable cholangiocarcinoma, PDT seems to be significantly superior to BS alone. PDT should be used as an adjunct to biliary stenting in these patients.展开更多
AIM:To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC). METHODS:This was a retrospective analysis of patients with hilar CC referred...AIM:To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC). METHODS:This was a retrospective analysis of patients with hilar CC referred to our institution from December, 1999 to January, 2011. Out of 232 patients, thirty-three patients with unresectable hilar CC were treated. Eighteen patients in the PDT group were treated with uncovered metal stents after one session of PDT. Fifteen patients in the control group were treated with metal stents alone. Porfimer sodium (2 mg/kg) was administered intravenously to PDT patients. Fortyeight hours later, PDT was administered using a diffusing fiber that was advanced across the tumor by either endoscopic retrograde cholangiopancreatography or percutaneous cholangiography. After performance of PDT, uncovered metal stents were inserted to ensure adequate decompression and bile drainage. Patient survival rates and cumulative stent patency were calculated using Kaplan-Meier analysis with the log-rank test. RESULTS:The PDT and control patients were comparable with respect to age, gender, health status, pretreatment bilirubin, and hilar CC stage. When compared to control, the PDT group was associated with significantly prolonged stent patency (median 244 ± 66 and 177 ± 45 d, respectively, P = 0.002) and longer patient survival (median 356 ± 213 and 230 ± 73 d, respectively, P = 0.006). Early complication rates were similar between the groups (PDT group 17%, control group 13%) and all patients were treated conservatively. Stent malfunctions occurred in 14 PDT patients (78%) and 12 control patients (80%). Of these 26 patients, twenty-two were treated endoscopically and four were treated with external drainage. CONCLUSION:Metal stenting after one session of PDT may be safe with acceptable complication rates. The PDT group was associated with a significantly longer stent patency than the control group in patients with unresectable hilar CC.展开更多
AIM： To investigate the anti-tumor effects of combined cytotoxic drug （gemcitabine） and photodynamic therapy （PDT） on human pancreatic cancer xenograft in nude mice.METHODS： Human pancreatic cancer cell line SW1...AIM： To investigate the anti-tumor effects of combined cytotoxic drug （gemcitabine） and photodynamic therapy （PDT） on human pancreatic cancer xenograft in nude mice.METHODS： Human pancreatic cancer cell line SW1990 was used in the investigation of the in vivo effect of combined gemcitabine and PDT on human pancreatic cancer xenograft in mice. Sixty mice were randomly allocated into a control group （without treatment）, photosensitizer treatment group （2 mg/kg photosan, without illumination）, chemotherapy group （50 mg/kg gemcitabine i.p.）, PDT group （2 mg/kg photosan ＋ laser irradiation） and combined treatment group （photosan ＋ chemotherapy）, with 12 mice in each group. Tumor size was measured twice every week. Anti-tumor activity in different groups was evaluated by tumor growth inhibition （TGI）RESULTS： No significant anti-tumor effect was observed either in photosensitizer treatment group or in chemotherapy group. PDT led to necrosis in cancer lesions and significantly reduced tumor volume compared with photosensitizer on day 6 and at the following time points after initialization of therapy （0.24 ± 0.15-0.49 ± 0.08 vs 0.43 ± 0.18-1.25± 0.09, P 〈 0.05）. PDT significantly reduced tumor volume in combined treatment group compared with photosensitizer treatment group （0.12 ± 0.07-0.28 ± 0.22 vs 0.39 ± 0.15-2.20 ± 0.12, P 〈 0.05）, small dose chemotherapy group （0.12 ± 0.07-0.28 ± 0.12 vs 0.32 ± 0.14-1.16 ± 0.08, P 〈 0.05） and control group （0.12 ± 0.07-0.28 ± 0.12 vs 0.43 ± 0.18-1.25 ± 0.09, P 〈 0.05）. TGI was higher in the combined treatment group （82.42%） than in the PDT group （58.18%）.CONCLUSION： PDT has a significant anti-tumor effect, which is maintained for a short time and can be significantly enhanced by small doses of gemcitabine.展开更多
Photodynamic therapy(PDT),as one of the noninvasive clinical cancer phototherapies,suffers from the key drawback associated with hypoxia at the tumor microenvironment(TME),which plays an important role in protecting t...Photodynamic therapy(PDT),as one of the noninvasive clinical cancer phototherapies,suffers from the key drawback associated with hypoxia at the tumor microenvironment(TME),which plays an important role in protecting tumor cells from damage caused by common treatments.High concentration of hydrogen peroxide(H2O2),one of the hallmarks of TME,has been recognized as a double-edged sword,posing both challenges,and opportunities for cancer therapy.The promising perspectives,strategies,and approaches for enhanced tumor therapies,including PDT,have been developed based on the fast advances in H2O2-enabled theranostic nanomedicine.In this review,we outline the latest advances in H2O2-responsive materials,including organic and inorganic materials for enhanced PDT.Finally,the challenges and opportunities for further research on H2O2-responsive anticancer agents are envisioned.展开更多
Objective:To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars(GNSs)with Chlorin e6 molecules(Ce6)into human peripheral blood mononuclear cells(PBMCs)-derived NK cells for tumo...Objective:To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars(GNSs)with Chlorin e6 molecules(Ce6)into human peripheral blood mononuclear cells(PBMCs)-derived NK cells for tumor targeted therapy.Methods:GNS@CaCO3/Ce6 nanoparticles were prepared and characterized by TEM and UV-vis.The cell surface markers and cytokines secretion of NK cells before and after loading the GNS@CaCO3/Ce6 nanoparticles were detected by Flow Cytometry(FCM)and ELISA.Effects of the GNS@CaCO3/Ce6-NK cells on A549 cancer cells was determined by FCM and CCK-8.Intracellular fluorescent signals of GNS@CaCO3/Ce6-NK cells were detected via Confocal laser scanning microscopic(CLSM)and FCM at different time points.Intracellular ROS generation of GNS@CaCO3/Ce6-NK cells under laser irradiation were examined by FCM.The distribution of GNS@CaCO3/Ce6-NK in A549 tumor-bearing mice were observed by fluorescence imaging and PA imaging.The combination therapy of GNS@CaCO3/Ce6-NK under laser irradiation were investigated on tumor-bearing mice.Results:The coated CaC03 shell on the surface of GNSs exhibited prominent delivery and protection effect of Ce6 during the cellular uptake process.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells possessed bimodal functions of fluorescence imaging and photoacoustic imaging.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells could actively target tumor tissues with the enhanced photothermal/photodynamic therapy and immunotherapy.Conclusions:The GNS@CaCO3/Ce6-NK shows effective tumor-targeting ability and prominent therapeutic efficacy toward lung cancer A549 tumor-bearing mice.Through fully utilizing the features of GNSs and NK cells,this new nanoplatform provides a new synergistic strategy for enhanced photothermal/photodynamic therapy and immunotherapy in the field of anticancer development in the near future.展开更多
Objective To investigate the efficacy and safety of photodynamic therapy （PDT） with topical 5-aminolaevulinic acid （ALA） on cervical condylomata acuminata. Methods Patients with cervical condylomata （n=30） were...Objective To investigate the efficacy and safety of photodynamic therapy （PDT） with topical 5-aminolaevulinic acid （ALA） on cervical condylomata acuminata. Methods Patients with cervical condylomata （n=30） were allocated into primary and recurrent group, and were given topical ALA under occlusive dressing for 3 hours followed by irradiation with semiconductor laser at a dose of 100 Jcm 2 and a power of 100 roW. The treatment was repeated 7 days later if the lesion was not completely removed after the first treatment. Complete response rate and recurrence rate of wart lesions as well as rate of adverse reaction were analyzed. Results The total complete response rate of PDT was 100% and the total recurrence rate was 5% after 3 months of follow-up. Recurrence rate of recurrent group was significantly lower than that of prior managements （100%, P〈0.01）. The side effects of PDT in patients mainly included mild burning and/or stinging restricted to the illuminated areas, and was significant lower than their own control （25% vs. 100%, P〈0.05）. Conclusion Compared with conventional therapies, topical application of ALA-PDT is a simple, effective, safe, well-tolerated, and low recurrence rate treatment for cervical condylomata acuminata.展开更多
Papillomatosis of the bile duct is a rare disease with a high risk of malignant transformation. Therapeutical options include partial hepatectomy and liver trans- plantation. A previously healthy 65-years old male dev...Papillomatosis of the bile duct is a rare disease with a high risk of malignant transformation. Therapeutical options include partial hepatectomy and liver trans- plantation. A previously healthy 65-years old male developed jaundice and right upper abdominal quadrant pain in 1996. A villous adenoma of the distal bile duct was diagnosed. A Whipple procedure was performed. In 2002 the patient turned symptomatic again. An- other adenoma was found in the right hepatic duct resulting in a right hepatectomy. Two years later the patient again developed cholestasis. Alter drainage of the left hepatic duct with a percutaneous transhepatic cholangial drainage （PTCD） catheter, a recurrent biliary adenomatosis was diagnosed by cholangioscopy. As there was no surgical option left, the patient received photodynamic therapy （PDT） for the recurrent biliary papillomatosis. Three mo alter he received further photodynamic therapies, the bile duct epithelium appeared normal and the patient had no signs of adenomatosis, both macroscopically and histologically. The follow-up cholangioscopy in late 2005 revealed only a small papil-loma without the need for intervention. In early 2006, the patient died of multi organ failure without signs of extrahepatic cholestasis or cholangitis at the age of 75, 10 years after the diagnosis of biliary papillomatosis was established. The patient exceeded the average life expectancy of patients with biliary papillomatosis by far. Thus, PDT might be a sufficient therapeutic option for recurrent papillomatosis patients with no significant side effects.展开更多
文摘Photodynamic therapy(PDT)can take place in the presence of three elements:Light with an appropriate wavelength;a photosensitizer;and the presence of oxygen.This type of treatment is very effective overall against bacterial,viral and mycotic cells.In the last 10 years many papers have been published on PDT with different types of photosensitizers(e.g.,methylene blue,toluidine blue,indocyanine green,curcumin-based photosensitizers),different wavelengths(e.g.,460 nm,630 nm,660 nm,810 nm)and various parameters(e.g.,power of the light,time of illumination,number of sessions).In the scientific literature all types of PDT seem very effective,even if it is difficult to find a standard protocol for each oral pathology.PDT could be an interesting way to treat some dangerous oral infections refractory to common pharmacological therapies,such as candidiasis from multidrug-resistant Candida spp.
基金supported by the National Natural Science Foundation of China(22171219 and 22222112)Innovation Talent Promotion Plan of Shaanxi Province for Science and Technology Innovation Team(2023-CX-TD-51)+2 种基金Key Laboratory Fund for Plasma Physics(6142A04210108)the Interdisciplinary Training Program for Doctoral Candidate of Xi’an Jiaotong University(IDT2105)National Natural Science Foundation NSAF Joint Fund(U2230112).
文摘The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy.Here,we report two perylene diimide-based metallacages that can form stable host–guest complexes with planar conjugated molecules including polycyclic aromatic hydrocarbons and photosensitizers(hypocrellin A).Such host–guest complexation not only prevents the aggregation of photosensitizers in aqueous environments,but also offers fluorescence resonance energy transfer(FRET)from the metallacage to the photosensitizers to further improve the singlet oxygen generation(Φ_(Δ)=0.66).The complexes are further assembled with amphiphilic polymers,forming nanoparticles with improved stability for anticancer study.Both in vitro and in vivo studies indicate that the nanoparticles display excellent anticancer activities upon light irradiation,showing great potential for cancer photodynamic therapy.This study provides a straightforward and effective approach for enhancing the photosensitivity of conventional photosensitizers via host–guest complexation-based FRET,which will open a new avenue for host–guest chemistry-based supramolecular theranostics.
基金National Natural Science Foundation of China,Grant/Award Numbers:22375066,U23A20594GuangDong Basic and Applied Basic Research Foundation,Grant/Award Numbers:2023B1515040003,2022A1515010315。
文摘Aggregate-level photodynamic therapy(PDT)has attracted significant interest and driven substantial advances in multifunction phototheranostic platforms.As exem-plified by two typical instances of aggregation-caused quenching of reactive oxygen species(ROS)and aggregation-induced generation of ROS,the aggregation effect plays a significant role on the ROS generation of photosensitizers(PSs),which is worthy of in-depth exploration and full utilization.However,in contrast to the well-developed researches on the aggregation effect on luminescence,the studies concerning the aggregation effect on ROS generation are currently in a relatively nascent and disjointed stage,lacking guidance from afirmly established research paradigm.To advance this regard,this review aims at providing a consolidated overview of the fundamental principles and research status of aggregation effects on the ROS generation.Here,the research status can be organized into two main facets.One involves the comparison between isolated state and aggregated state,which is mainly conducted by two methods of changing solvent environments and adding adjuvants into a given solvent.The other underscores the distinctions between different aggregate states,consisting of three parts,namely comparison within the same or between different categories based on the classification of single-component and multicomponent aggregates.In this endeavor,we will present our views on cur-rent research methodologies that explore how aggregation affects ROS generation and highlight the design strategies to leverage the aggregation effect to optimize PS regiments.We aspire this review to propel the advancement of phototheranostic plat-forms and accelerate the clinical implementation of precision medicine,and inspire more contributions to aggregate-level photophysics and photochemistry,pushing the aggregate science and materials forward.
基金NSFC,Grant/Award Numbers:52073045,51773195Key Scientific and Technological Project of Jilin Province,Grant/Award Number:20190701010GH+2 种基金Development and Reform Commission of Jilin Province,Grant/Award Number:2020C035-5Changchun Science and Technology Bureau,Grant/Award Number:21ZGY19EPSRC,Grant/Award Number:EP/L02621X/1。
文摘Currently three major problems seriously limit the practical application of can-cer photodynamic therapy(PDT):(i)the hypoxic tumor microenvironment(TME);(ii)low generation efficiency of toxic reactive oxygen species(ROS)in aggre-gates and(iii)shallow tissue penetration depth of excitation light.Very limited approaches are available for addressing all the above three problems with a single design.Herein,a rational“three birds with one stone”molecular and nanoengi-neering strategy is demonstrated:a photodynamic nanoplatform U-Ir@PAA-ABS based on the covalent combination of lanthanide-doped upconversion nanoparti-cles(UCNPs)and an AIE-active dinuclear Ir(III)complex provides a low oxygen concentration-dependent type-I photochemical process upon 980 nm irradiation by Föster resonance energy transfer(FRET).U-Ir@PAA-ABS targets mitochondria and has excellent phototoxicity even in severe hypoxia environments upon 980 nm irradiation,inducing a dual-mode cell death mechanism by apoptosis and ferropto-sis.Taken together,the in vitro and in vivo results demonstrate a successful strategy for improving the efficacy of PDT against hypoxic tumors.
基金supported by the Applied Basic Research Project of Shanxi Province(201901D211470)Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi Province(201802093)The National Natural Science Foundation of China(No.81773765).
文摘Photodynamic therapy(PDT)is a promising cancer treatment.This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]−10,15,20-triphenyl-porphyrin(DTP)mediated PDT(DTP-PDT).Cell viability,reactive oxygen species(ROS),and apoptosis were measured with a Cell Counting Kit-8 assay,DCFH-DA fluorescent probe,and Hoechst staining,respectively.Cell apoptosis-and autophagy-related proteins were examined using western blotting.RNA sequencing was used to screen differentially expressed mRNAs(DERs),and bioinformatic analysis was performed to identify the major biological events after DTP-PDT.Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells.The ROS scavenger N-acetyl-L-cysteine(NAC)and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity.DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2,which could also be inhibited by NAC or SB203580.The level of LC3B-Ⅱ,a marker of autophagy,was increased by DTP-PDT.A total of 3496 DERs were obtained after DTP-PDT.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes,the nuclear lumen,protein binding,cell cycle,protein targeting to the endoplasmic reticulum,and ribosomal DNA replication.Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints.Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes.Therefore,DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy,partly through ROS and the P38 MAPK signaling pathway.Genes associated with the cell cycle,ribosomes,DNA replication,and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.
基金supported by China Medical University’s High-level Talents Research Start-up Fund(1210619010)Double First-Class Scientific Research Fund(3110210603).
文摘Current antitumor monotherapy has many limitations,highlighting the need for novel synergistic anticancer strategies.Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory role in tumorigenesis and treatment.Photodynamic therapy(PDT)causes irreversible chemical damage to target lesions and is widely used in antitumor therapy.However,PDT’s effectiveness is usually hindered by several obstacles,such as hypoxia,excess glutathione(GSH),and tumor resistance.Ferroptosis improves the anticancer efficacy of PDT by increasing oxygen and reactive oxygen species(ROS)or reducing GSH levels,and PDT also enhances ferroptosis induction due to the ROS effect in the tumor microenvironment(TME).Strategies based on nanoparticles(NPs)can subtly exploit the potential synergy of ferroptosis and PDT.This review explores recent advances and current challenges in the landscape of the underlyingmechanisms regulating ferroptosis and PDT,as well as nano delivery system-mediated synergistic anticancer activity.These include polymers,biomimetic materials,metal organic frameworks(MOFs),inorganics,and carrier-free NPs.Finally,we highlight future perspectives of this novel emerging paradigm in targeted cancer therapies.
文摘Photodynamic therapy(PDT)is applied as a robust therapeutic option for tumor,which exhibits some advantages of unique selectivity and irreversible damage to tumor cells.Among which,photosensitizer(PS),appropriate laser irradiation and oxygen(O_(2))are three essential components for PDT,but the hypoxic tumor microenvironment(TME)restricts the O_(2) supply in tumor tissues.Even worse,tumor metastasis and drug resistance frequently happen under hypoxic condition,which further deteriorate the antitumor effect of PDT.To enhance the PDT efficiency,critical attention has been received by relieving tumor hypoxia,and innovative strategies on this topic continue to emerge.Traditionally,the O_(2) supplement strategy is considered as a direct and effective strategy to relieve TME,whereas it is confronted with great challenges for continuous O_(2) supply.Recently,O_(2)-independent PDT provides a brand new strategy to enhance the antitumor efficiency,which can avoid the influence of TME.In addition,PDT can synergize with other antitumor strategies,such as chemotherapy,immunotherapy,photothermal therapy(PTT)and starvation therapy,to remedy the inadequate PDT effect under hypoxia conditions.In this paper,we summarized the latest progresses in the development of innovative strategies to improve PDT efficacy against hypoxic tumor,which were classified into O_(2)-dependent PDT,O_(2)-independent PDT and synergistic therapy.Furthermore,the advantages and deficiencies of various strategies were also discussed to envisage the prospects and challenges in future study.
基金supported by the Natural Science Foundation of Gansu Province(22JR5RA496,22JR5RA955)Talent Innovation and Entrepreneurship Project of Lanzhou City(2022-RC-49)+4 种基金Talent Innovation and Entrepreneurship Project of Chengguan District(2022-rc-7)Foundation of Lanzhou University Second Hospital(CYXZ2022-22)Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital(CY2021-QN-A02)Fundamental Research Funds for the Central Universities(lzujbky-2022-50)Project of Gansu Province Health Commission(GSWSKY2022-02)Innovation Fund for Colleges and Universities(2021B-046).
文摘Background:((1-triphenylaminebenzo[c][1,2,5]thiadiazole-4-yl)styryl)-1-methylpyridin methylpyridin-1-ium iodide salt(TBZPy)is a novel photosensitizer that displays excellent photodynamic properties.However,There are few reports on the mechanism of action of the TBZPy photodynamic.Previous studies revealed that photodynamic therapy(PDT)could induce endoplasmic reticulum stress by acting on the endoplasmic reticulum.Therefore,in this study,we investigated the effects of endoplasmic reticulum stress induced by TBZPy-PDT in treating High-risk human papillomavirus(HR-HPV)infection and their underlying mechanisms.Methods:The human cervical cancer cell line HeLa(containing whole genome of HR-HPV18)was treated with TBZPy-PDT.Cell migration,invasion,and colony-forming ability were evaluated using wound-healing,Transwell invasion,and colonyforming assays,respectively.Through western blot analysis,we determined the level of expression of the PI3K/AKT and PERK/eIF2αpathway proteins and the proteins associated with calcium trafficking and apoptosis.The calcium levels in the cytoplasm were detected via flow cytometry.Results:The result shows that TBZPy-PDT could inhibite the migration,invasion,and colony forming ability of infected HeLa cells by downregulating the PI3K/AKT pathway in vitro.And we found that TBZPy-PDT induced endoplasmic reticulum stress-specific apoptosis via the PERK/eIF2αpathway.Moreover,TBZPy-PDT increased the levels of calcium and calmodulin,while decreasing the levels of endoplasmic reticulum calcium-binding proteins.Conclusions:TBZPy-PDT is effective on treating human papillomavirus-infected cells.Targeting the PI3K/AKT and PERK/eIF2αpathways and the endoplasmic reticulum stress process may help improve the effects of TBZPy-PDT for treating high-risk human papillomavirus infection.
基金the National Natural Science Foundation of China(grant no.81971847)Interdisciplinary Program of Shanghai Jiao Tong University(grant no.YG2019QNB10)+1 种基金Shanghai Municipal Key Clinical Specialty(grant no.shslczdzk00901)Shanghai Municipal Commission of Health and Family Planning(grant no.202240150)。
文摘Port-wine stain(PWS)is a congenital capillary malformation that occurs in 0.3%–0.5%of newborns.The pulsed dye laser is the current gold standard treatment for PWS;however,its efficacy is poor.Photosensitizer photodynamic therapy(PDT)is considered a promising treatment for PWS.Here we provide a comprehensive overview of PDT.
文摘Objective： To evaluate the clinical effectiveness and adverse effects of photodynamic therapy （PDT） for the upper gastrointestinal tract cancers. Methods： 56 patients with upper gastrointestinal cancers in different clinical stages were treated with PDT. Diode laser （630 nm） was used as the light source and the parameters were as follows： power density 200 to 400 mW/cm, energy density 100 to 300 J/cm. PHOTOFRIN was used as photosensitizer, which was given in a dose of 2 mg/kg intravenously 12-24 h before irradiation. Results： Evaluation of the 56 patients＇ therapeutic effectiveness showed that 6 patients （10.7%） had a complete response （CR）, 33 patients （58.9%） partial response （PR）, 12 patients （21.4%） mild response （MR）, and 5 patients （8.9%） no response （NR）. The total response rate （CR＋PR） was 69.6%. No patients had severe adverse effects in this group. Conclusion： PDT is an effective and safe palliative modality for upper gastrointestinal tract cancers.
文摘AIM:To compare the efficacy of low-fluence photodynamic therapy(PDT) combinations in the treatment of age-related macular degeneration(AMD).· METHODS:Forty-five previously untreated eyes of 45 patients with exudative AMD whose best-corrected visual acuity(BCVA) was ≥0.3(Snellen) were enrolled.15 patients in Group I underwent low-fluence PDT(25J/cm2-300mW/cm2-83sec) and intravitreal pegaptanib combination,15 patients in Group II underwent PDT(50J/cm2-600mW/cm2-83sec) and intravitreal pegaptanib combination while,15 patients in Group III underwent intravitreal pegaptanib monotherapy.Complete ophthalmologic examinations were performed in pre and post treatment visits,and the results were statistically analised.A clinical activity score(CAS) was calculated by using changes in lesion size,amount of hemorrhage,staining pattern in FA and OCT measurement of intra/subretinal fluid.≤3 logMAR lines of decrease in BCVA and decrease in CAS were considered as successful treatment.· RESULTS:The mean age of 19 female(42.2%) and 26 male(57.8%) patients was(72.82±8.02) years.Mean follow-up was(13.93±5.87) months.Lesion type was occult in 28 eyes(62.2%).Treatment success rates according to BCVA assessments were 86.7%,80%,60% and mean BCVA decrease were 0.3,1.0,2.2 logMAR lines in Group I,II and III,respectively(P >0.05).According to the changes in central macular thickness and CAS,no difference was found among the study groups(P =0.850 and P =0.811,respectively).Patients treated with combination regimens had lower intravitreal injection frequencies(P =0.015).· CONCLUSION:Combination regimen with intravitreal pegaptanib and low-fluence PDT seems to be safe and effective in stabilizing the clinical activity and BCVA in exudative AMD.·
文摘To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma.METHODSIncluded studies compared outcomes with photodynamic therapy and biliary stenting (PDT group) vs biliary stenting only (BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubMed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I<sup>2</sup> statistic.RESULTSTen studies (n = 402) that met inclusion criteria were included in this analysis. The P for χ<sup>2</sup> heterogeneity for all the pooled accuracy estimates was > 0.10. Pooled odds ratio for successful biliary drainage (decrease in bilirubin level > 50% within 7days after stenting) in PDT vs BS group was 4.39 (95%CI: 2.35-8.19). Survival period in PDT and BS groups were 413.04 d (95%CI: 349.54-476.54) and 183.41 (95%CI: 136.81-230.02) respectively. The change in Karnofsky performance scores after intervention in PDT and BS groups were +6.99 (95%CI: 4.15-9.82) and -3.93 (95%CI: -8.63-0.77) respectively. Odds ratio for post-intervention cholangitis in PDT vs BS group was 0.57 (95%CI: 0.35-0.94). In PDT group, 10.51% (95%CI: 6.94-14.72) had photosensitivity reactions that were self-limiting. Subgroup analysis of prospective studies showed similar results, except the incidence of cholangitis was comparable in both groups.CONCLUSIONIn palliation of unresectable cholangiocarcinoma, PDT seems to be significantly superior to BS alone. PDT should be used as an adjunct to biliary stenting in these patients.
文摘AIM:To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC). METHODS:This was a retrospective analysis of patients with hilar CC referred to our institution from December, 1999 to January, 2011. Out of 232 patients, thirty-three patients with unresectable hilar CC were treated. Eighteen patients in the PDT group were treated with uncovered metal stents after one session of PDT. Fifteen patients in the control group were treated with metal stents alone. Porfimer sodium (2 mg/kg) was administered intravenously to PDT patients. Fortyeight hours later, PDT was administered using a diffusing fiber that was advanced across the tumor by either endoscopic retrograde cholangiopancreatography or percutaneous cholangiography. After performance of PDT, uncovered metal stents were inserted to ensure adequate decompression and bile drainage. Patient survival rates and cumulative stent patency were calculated using Kaplan-Meier analysis with the log-rank test. RESULTS:The PDT and control patients were comparable with respect to age, gender, health status, pretreatment bilirubin, and hilar CC stage. When compared to control, the PDT group was associated with significantly prolonged stent patency (median 244 ± 66 and 177 ± 45 d, respectively, P = 0.002) and longer patient survival (median 356 ± 213 and 230 ± 73 d, respectively, P = 0.006). Early complication rates were similar between the groups (PDT group 17%, control group 13%) and all patients were treated conservatively. Stent malfunctions occurred in 14 PDT patients (78%) and 12 control patients (80%). Of these 26 patients, twenty-two were treated endoscopically and four were treated with external drainage. CONCLUSION:Metal stenting after one session of PDT may be safe with acceptable complication rates. The PDT group was associated with a significantly longer stent patency than the control group in patients with unresectable hilar CC.
文摘AIM： To investigate the anti-tumor effects of combined cytotoxic drug （gemcitabine） and photodynamic therapy （PDT） on human pancreatic cancer xenograft in nude mice.METHODS： Human pancreatic cancer cell line SW1990 was used in the investigation of the in vivo effect of combined gemcitabine and PDT on human pancreatic cancer xenograft in mice. Sixty mice were randomly allocated into a control group （without treatment）, photosensitizer treatment group （2 mg/kg photosan, without illumination）, chemotherapy group （50 mg/kg gemcitabine i.p.）, PDT group （2 mg/kg photosan ＋ laser irradiation） and combined treatment group （photosan ＋ chemotherapy）, with 12 mice in each group. Tumor size was measured twice every week. Anti-tumor activity in different groups was evaluated by tumor growth inhibition （TGI）RESULTS： No significant anti-tumor effect was observed either in photosensitizer treatment group or in chemotherapy group. PDT led to necrosis in cancer lesions and significantly reduced tumor volume compared with photosensitizer on day 6 and at the following time points after initialization of therapy （0.24 ± 0.15-0.49 ± 0.08 vs 0.43 ± 0.18-1.25± 0.09, P 〈 0.05）. PDT significantly reduced tumor volume in combined treatment group compared with photosensitizer treatment group （0.12 ± 0.07-0.28 ± 0.22 vs 0.39 ± 0.15-2.20 ± 0.12, P 〈 0.05）, small dose chemotherapy group （0.12 ± 0.07-0.28 ± 0.12 vs 0.32 ± 0.14-1.16 ± 0.08, P 〈 0.05） and control group （0.12 ± 0.07-0.28 ± 0.12 vs 0.43 ± 0.18-1.25 ± 0.09, P 〈 0.05）. TGI was higher in the combined treatment group （82.42%） than in the PDT group （58.18%）.CONCLUSION： PDT has a significant anti-tumor effect, which is maintained for a short time and can be significantly enhanced by small doses of gemcitabine.
基金supported by NNSF of China (61525402, 61775095, 51803091, 61935004)Jiangsu Provincial key research and development plan (BE2017741)Six talent peak innovation team in Jiangsu Province (TD-SWYY-009)
文摘Photodynamic therapy(PDT),as one of the noninvasive clinical cancer phototherapies,suffers from the key drawback associated with hypoxia at the tumor microenvironment(TME),which plays an important role in protecting tumor cells from damage caused by common treatments.High concentration of hydrogen peroxide(H2O2),one of the hallmarks of TME,has been recognized as a double-edged sword,posing both challenges,and opportunities for cancer therapy.The promising perspectives,strategies,and approaches for enhanced tumor therapies,including PDT,have been developed based on the fast advances in H2O2-enabled theranostic nanomedicine.In this review,we outline the latest advances in H2O2-responsive materials,including organic and inorganic materials for enhanced PDT.Finally,the challenges and opportunities for further research on H2O2-responsive anticancer agents are envisioned.
基金supported from 973 Project (Grant No. 2015CB931802 and 2017YFA0205301)Chinese National Natural Scientific Fund (Grant No.81327002 and 81803094)+1 种基金China Postdoctoral Science Foundation (Grant No. 2017M621486)Funding from Shanghai Engineering Research Center for Intelligent diagnosis and treatment instrument (Grant No.15DZ2252000)
文摘Objective:To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars(GNSs)with Chlorin e6 molecules(Ce6)into human peripheral blood mononuclear cells(PBMCs)-derived NK cells for tumor targeted therapy.Methods:GNS@CaCO3/Ce6 nanoparticles were prepared and characterized by TEM and UV-vis.The cell surface markers and cytokines secretion of NK cells before and after loading the GNS@CaCO3/Ce6 nanoparticles were detected by Flow Cytometry(FCM)and ELISA.Effects of the GNS@CaCO3/Ce6-NK cells on A549 cancer cells was determined by FCM and CCK-8.Intracellular fluorescent signals of GNS@CaCO3/Ce6-NK cells were detected via Confocal laser scanning microscopic(CLSM)and FCM at different time points.Intracellular ROS generation of GNS@CaCO3/Ce6-NK cells under laser irradiation were examined by FCM.The distribution of GNS@CaCO3/Ce6-NK in A549 tumor-bearing mice were observed by fluorescence imaging and PA imaging.The combination therapy of GNS@CaCO3/Ce6-NK under laser irradiation were investigated on tumor-bearing mice.Results:The coated CaC03 shell on the surface of GNSs exhibited prominent delivery and protection effect of Ce6 during the cellular uptake process.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells possessed bimodal functions of fluorescence imaging and photoacoustic imaging.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells could actively target tumor tissues with the enhanced photothermal/photodynamic therapy and immunotherapy.Conclusions:The GNS@CaCO3/Ce6-NK shows effective tumor-targeting ability and prominent therapeutic efficacy toward lung cancer A549 tumor-bearing mice.Through fully utilizing the features of GNSs and NK cells,this new nanoplatform provides a new synergistic strategy for enhanced photothermal/photodynamic therapy and immunotherapy in the field of anticancer development in the near future.
文摘Objective To investigate the efficacy and safety of photodynamic therapy （PDT） with topical 5-aminolaevulinic acid （ALA） on cervical condylomata acuminata. Methods Patients with cervical condylomata （n=30） were allocated into primary and recurrent group, and were given topical ALA under occlusive dressing for 3 hours followed by irradiation with semiconductor laser at a dose of 100 Jcm 2 and a power of 100 roW. The treatment was repeated 7 days later if the lesion was not completely removed after the first treatment. Complete response rate and recurrence rate of wart lesions as well as rate of adverse reaction were analyzed. Results The total complete response rate of PDT was 100% and the total recurrence rate was 5% after 3 months of follow-up. Recurrence rate of recurrent group was significantly lower than that of prior managements （100%, P〈0.01）. The side effects of PDT in patients mainly included mild burning and/or stinging restricted to the illuminated areas, and was significant lower than their own control （25% vs. 100%, P〈0.05）. Conclusion Compared with conventional therapies, topical application of ALA-PDT is a simple, effective, safe, well-tolerated, and low recurrence rate treatment for cervical condylomata acuminata.
文摘Papillomatosis of the bile duct is a rare disease with a high risk of malignant transformation. Therapeutical options include partial hepatectomy and liver trans- plantation. A previously healthy 65-years old male developed jaundice and right upper abdominal quadrant pain in 1996. A villous adenoma of the distal bile duct was diagnosed. A Whipple procedure was performed. In 2002 the patient turned symptomatic again. An- other adenoma was found in the right hepatic duct resulting in a right hepatectomy. Two years later the patient again developed cholestasis. Alter drainage of the left hepatic duct with a percutaneous transhepatic cholangial drainage （PTCD） catheter, a recurrent biliary adenomatosis was diagnosed by cholangioscopy. As there was no surgical option left, the patient received photodynamic therapy （PDT） for the recurrent biliary papillomatosis. Three mo alter he received further photodynamic therapies, the bile duct epithelium appeared normal and the patient had no signs of adenomatosis, both macroscopically and histologically. The follow-up cholangioscopy in late 2005 revealed only a small papil-loma without the need for intervention. In early 2006, the patient died of multi organ failure without signs of extrahepatic cholestasis or cholangitis at the age of 75, 10 years after the diagnosis of biliary papillomatosis was established. The patient exceeded the average life expectancy of patients with biliary papillomatosis by far. Thus, PDT might be a sufficient therapeutic option for recurrent papillomatosis patients with no significant side effects.
