The use of bacteria to specifically migrate to cancerous tissue and elicit an antitumor immune response provides a promising platform against cancer with significantly high potency.With dozens of clinical trials under...The use of bacteria to specifically migrate to cancerous tissue and elicit an antitumor immune response provides a promising platform against cancer with significantly high potency.With dozens of clinical trials underway,some researchers hold the following views:“humans are nearing the first commercial live bacteria therapeutic.”However,the facultative anaerobe Salmonella typhimurium VNP20009,which is particularly safe and shows anticancer effects in preclinical studies,had failed in a phase I clinical trial due to low tumor regression and undesired dose-dependent side effects.This is almost certain to disappoint people’s inflated expectations,but it is noted that recent stateof-the-art research has turned attention to bacteria-mediated synergistic cancer therapy(BMSCT).In this review,the foundation of bacteria-mediated bio-therapy is outlined.Then,we summarize the potential benefits and challenges of bacterial bio-therapy in combination with different traditional anticancer therapeutic modalities(chemotherapy,photothermal therapy,reactive oxygen and nitrogen species therapy,immunotherapy,or prodrug-activating therapy)in the past 5 years.Next,we discuss multiple administration routes of BMSCT,highlighting potentiated antitumor responses and avoidance of potential side effects.Finally,we envision the opportunities and challenges for BMSCT development,with the purpose of inspiring medicinal scientists to widely utilize the microbiome approach in patient populations.展开更多
Synergistic therapy combines multiple therapeutic approaches in one shot,thus could significantly amplify the therapeutic effects.However,how to design the desirable combination to maximize the synergistic effect is s...Synergistic therapy combines multiple therapeutic approaches in one shot,thus could significantly amplify the therapeutic effects.However,how to design the desirable combination to maximize the synergistic effect is still a big challenge in cancer management.Herein,a nanoagent composed of glucose oxidase(GOx)and upconversion nanoparticles(UCNPs)were constructed for programmable starving-photodynamic synergistic cancer therapy through cascade glucose oxidation and hydrogen peroxide photolysis.In this nanoagent,GOx modulated the tumor glucose metabolism and consumed the β-D-glucose to produce H2O2.The glucose depletion induced"starvation"in cancer cells and caused cell death.Afterwards,the generated H2O2 was photolyzed by the invisible ultraviolet emission of UCNPs under near-infrared light excitation at 980 nm.The toxic hydroxyl radicals produced by photolysis further induced cancer cell death.Both in vitro and in vivo experiments confirmed that this starving-photodynamic synergistic therapy significantly outran any single therapy.This study paves an avenue to design programmable starving-photodynamic synergistic therapy for cancer management.展开更多
The therapeutic strategy that gives consideration to the combination of photodynamic therapy and chemotherapy,has emerged as a potential development of effective anti-cancer medicine.Nevertheless,co-delivery of photos...The therapeutic strategy that gives consideration to the combination of photodynamic therapy and chemotherapy,has emerged as a potential development of effective anti-cancer medicine.Nevertheless,co-delivery of photosensitizers(PSs)and chemotherapeutic drugs in traditional carriers still remains great limitations due to low drug loadings and poor biocompatibility.Herein,we have utilized a computer-aided strategy to achieve a desired carrier-free self-delivery of pyropheophorbide a(PPa,a common PS)and podophyllotoxin(PPT,a classical chemotherapeutic drug)for synergistic cancer therapy.First,the computational simulation method identified the similar molecular sizes and rigid molecular structures between two drugs molecules.Based on the molecular docking,the intermolecular interactions were found to includeπ-πstackings,hydrophobic interactions and hydrogen bonds.Next,both drugs could co-assemble into nanoparticles(NPs)via one-step nanoprecipitation method.The various spectral experiments(UV,IR and FL)were conducted to evaluate the formation mechanism of spherical NPs.Moreover,in vitro and in vivo experiments systematically demonstrated that PPT/PPa NPs not only showed better cellular uptake efficiency,stronger cytotoxicity and higher accumulation in tumor sites,but also exhibited synergistic antitumor effect in female BALB/C bearing-4T1 tumor mice.Such a computer-aided design strategy of chem-photodynamic drugs self-delivery systems pave the way for efficient synergistic cancer therapy.展开更多
Mitochondria are the power plants of the cell and play key roles in activating the apoptotic pathway in cancer cells,which are readily susceptible to cytotoxic reactive oxygen species and temperature elevations.Herein...Mitochondria are the power plants of the cell and play key roles in activating the apoptotic pathway in cancer cells,which are readily susceptible to cytotoxic reactive oxygen species and temperature elevations.Herein,we develop a"nanomissile"that targets mitochondria to enhance tumor treatment effects by facilitating mitochondrial dysfunction and releasing cytochrome C to activate the apoptotic pathway of cancer cells under 650-nm laser irradiation.Porphyringrafted polydopamine nanomaterial(PTPF-MitP)is designed as a nanomissile,with integrated O;-evolving photodynamic therapy and moderate photothermal therapy,which can selectively deliver to the mitochondria through a targeting unit,MitP.The cytotoxicity of PTPF-MitP to human lung tumor cells is twice as high as that of PTPF that does not have mitochondrial targeting units.In addition,it represents a realtime visualization and highly efficient treatment for tumor sites in vivo.This development represents a viable strategy for cancer therapy.展开更多
Ferroptosis offers a novel method for overcoming therapeutic resistance of cancers to conventional cancer treatment regimens.Its effective use as a cancer therapy requires a precisely targeted approach,which can be fa...Ferroptosis offers a novel method for overcoming therapeutic resistance of cancers to conventional cancer treatment regimens.Its effective use as a cancer therapy requires a precisely targeted approach,which can be facilitated by using nanoparticles and nanomedicine,and their use to enhance ferroptosis is indeed a growing area of research.While a few review papers have been published on iron-dependent mechanism and inducers of ferroptosis cancer therapy that partly covers ferroptosis nanoparticles,there is a need for a comprehensive review focusing on the design of magnetic nanoparticles that can typically supply iron ions to promote ferroptosis and simultaneously enable targeted ferroptosis cancer nanomedicine.Furthermore,magnetic nanoparticles can locally induce ferroptosis and combinational ferroptosis with diagnostic magnetic resonance imaging(MRI).The use of remotely controllable magnetic nanocarriers can offer highly effective localized image-guided ferroptosis cancer nanomedicine.Here,recent developments in magnetically manipulable nanocarriers for ferroptosis cancer nanomedicine with medical imaging are summarized.This review also highlights the advantages of current state-of-the-art image-guided ferroptosis cancer nanomedicine.Finally,image guided combinational ferroptosis cancer therapy with conventional apoptosis-based therapy that enables synergistic tumor therapy is discussed for clinical translations.展开更多
The injectable self-healing polysaccharide hydrogel was prepared by the formation of Schiff base bonds between aldehyde-modified methylcellulose(MC–CHO)and carboxymethyl chitosan(CMC).The copper sulfide nanoparticles...The injectable self-healing polysaccharide hydrogel was prepared by the formation of Schiff base bonds between aldehyde-modified methylcellulose(MC–CHO)and carboxymethyl chitosan(CMC).The copper sulfide nanoparticles(CuS NPs)and pH-sensitive doxorubicin-loaded zeolitic imidazolate frameworks nanoparticles(DOX@ZIF-8 NPs)were prepared and could be well-dispersed into the hydrogel system.The presence of CuS NPs can achieve photothermal therapy(PTT)for tumors under the irradiation of the near-infrared(NIR)laser.Moreover,CuS NPs can generate photodynamic effects under NIR irradiation,converting oxygen into toxic reactive oxygen species(ROS)and presenting efficient photodynamic therapy(PDT).The DOX@ZIF-8 NPs can be decomposed under an intracellular acidic environment and realize the controlled release of DOX.The injectable self-healing hydrogel loading Cu S and DOX@ZIF-8 NPs can achieve synergistic photothermal-photodynamic-chemo therapy for tumors and will inspire the researchers to construct a platform from hydrogel combined with multifunctional nanomaterials to realize the effective multimodal therapy for tumor.展开更多
Multifunctional core-shell nanostructures formed by integration of distinct components have received wide attention as promising biological platforms in recent years. In this work, crystalline zeolitic imidazolate fra...Multifunctional core-shell nanostructures formed by integration of distinct components have received wide attention as promising biological platforms in recent years. In this work, crystalline zeolitic imidazolate framework-8 （ZIF-8）, a typical metal-organic framework （MOF）, is coated onto single gold nanorod （AuNR） core for successful realization of synergistic photothermal and chemotherapy triggered by near-infrared （NIR） light. Impressivel）~ high doxorubicin hydrochloride （DOX） loading capacity followed by pH and NIR light dual stimuli-responsive DOX release can be easily implemented through formation and breakage of coordination bonds in the system. Moreover, under NIR laser irradiation at 808 nm, these novel AuNR@MOF core-shell nanostructures exhibit effective synergistic chemo-photothermal therapy both in vitro and in vivo, confirmed by cell treatment and tumor ablation via intravenous injection.展开更多
Direct administration of drugs and genes to the lungs by pulmonary delivery offers a potential effective therapy for lung cancers.In this study,combined doxorubicin（DOX） and Bcl2 siRNA was employed for cancer therap...Direct administration of drugs and genes to the lungs by pulmonary delivery offers a potential effective therapy for lung cancers.In this study,combined doxorubicin（DOX） and Bcl2 siRNA was employed for cancer therapy using polyethylenimine（PEI） as the carrier of Bcl2 siRNA.Most of the DOX and siRNA possessed high cellular uptake efficiency in B16F10 cells,which was proved by FCM and CLSM analysis.Real-time PCR showed that PEI/Bcl2 siRNA exhibited high gene silencing efficiency with 70%Bcl2 mRNA being knocked down.The combination of DOX and siRNA could enhance the cell proliferation inhibition and the cell apoptosis against B16F10 cells compared to free DOX or PEI/Bcl2 siRNA.Furthermore,the biodistribution of DOX and siRNA via pulmonary administration was studied in mice with B16F10 metastatic lung cancer.The results showed that most of the DOX and siRNA were accumulated in lungs and lasted at least for 3 days,which suggested that combined DOX and siRNA by pulmonary administration may have high anti-tumor effects for metastatic lung cancer treatment in vivo.展开更多
基金Supported by National Natural Science Foundation of China,No.81773656Liaoning Revitalization Talents Program,No.XLYC1808017Shenyang Youth Science and Technology Innovation Talents Program,No.RC190454.
文摘The use of bacteria to specifically migrate to cancerous tissue and elicit an antitumor immune response provides a promising platform against cancer with significantly high potency.With dozens of clinical trials underway,some researchers hold the following views:“humans are nearing the first commercial live bacteria therapeutic.”However,the facultative anaerobe Salmonella typhimurium VNP20009,which is particularly safe and shows anticancer effects in preclinical studies,had failed in a phase I clinical trial due to low tumor regression and undesired dose-dependent side effects.This is almost certain to disappoint people’s inflated expectations,but it is noted that recent stateof-the-art research has turned attention to bacteria-mediated synergistic cancer therapy(BMSCT).In this review,the foundation of bacteria-mediated bio-therapy is outlined.Then,we summarize the potential benefits and challenges of bacterial bio-therapy in combination with different traditional anticancer therapeutic modalities(chemotherapy,photothermal therapy,reactive oxygen and nitrogen species therapy,immunotherapy,or prodrug-activating therapy)in the past 5 years.Next,we discuss multiple administration routes of BMSCT,highlighting potentiated antitumor responses and avoidance of potential side effects.Finally,we envision the opportunities and challenges for BMSCT development,with the purpose of inspiring medicinal scientists to widely utilize the microbiome approach in patient populations.
基金financially supported by the National Natural Science Foundation of China (21807073, 31771036 and 51703132)the Basic Research Program of Shenzhen (JCYJ20170818144745087, JCYJ20180507182413022 and JCYJ20170412111100742)+2 种基金Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project (2018B030308003)Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China (161032)China Postdoctoral Science Foundation (2018M630987 and 2019T120752)
文摘Synergistic therapy combines multiple therapeutic approaches in one shot,thus could significantly amplify the therapeutic effects.However,how to design the desirable combination to maximize the synergistic effect is still a big challenge in cancer management.Herein,a nanoagent composed of glucose oxidase(GOx)and upconversion nanoparticles(UCNPs)were constructed for programmable starving-photodynamic synergistic cancer therapy through cascade glucose oxidation and hydrogen peroxide photolysis.In this nanoagent,GOx modulated the tumor glucose metabolism and consumed the β-D-glucose to produce H2O2.The glucose depletion induced"starvation"in cancer cells and caused cell death.Afterwards,the generated H2O2 was photolyzed by the invisible ultraviolet emission of UCNPs under near-infrared light excitation at 980 nm.The toxic hydroxyl radicals produced by photolysis further induced cancer cell death.Both in vitro and in vivo experiments confirmed that this starving-photodynamic synergistic therapy significantly outran any single therapy.This study paves an avenue to design programmable starving-photodynamic synergistic therapy for cancer management.
基金This work was supported by National Natural Science Foundation of China(nos.81872816,81773656,U1608283)Liaoning Revitalization Talents Program,No XLYC1808017.
文摘The therapeutic strategy that gives consideration to the combination of photodynamic therapy and chemotherapy,has emerged as a potential development of effective anti-cancer medicine.Nevertheless,co-delivery of photosensitizers(PSs)and chemotherapeutic drugs in traditional carriers still remains great limitations due to low drug loadings and poor biocompatibility.Herein,we have utilized a computer-aided strategy to achieve a desired carrier-free self-delivery of pyropheophorbide a(PPa,a common PS)and podophyllotoxin(PPT,a classical chemotherapeutic drug)for synergistic cancer therapy.First,the computational simulation method identified the similar molecular sizes and rigid molecular structures between two drugs molecules.Based on the molecular docking,the intermolecular interactions were found to includeπ-πstackings,hydrophobic interactions and hydrogen bonds.Next,both drugs could co-assemble into nanoparticles(NPs)via one-step nanoprecipitation method.The various spectral experiments(UV,IR and FL)were conducted to evaluate the formation mechanism of spherical NPs.Moreover,in vitro and in vivo experiments systematically demonstrated that PPT/PPa NPs not only showed better cellular uptake efficiency,stronger cytotoxicity and higher accumulation in tumor sites,but also exhibited synergistic antitumor effect in female BALB/C bearing-4T1 tumor mice.Such a computer-aided design strategy of chem-photodynamic drugs self-delivery systems pave the way for efficient synergistic cancer therapy.
基金supported by the National Natural Science Foundation of China(21705117,22174110,21904095 and 22004089)the Elite Scholar Program of Tianjin University(2019XRG-0065)+2 种基金the Program of Tianjin Science and Technology Major Project and Engineering(19ZXYXSY00090)the Program for Chang Jiang Scholars and Innovative Research Team,Ministry of Education,China(IRT-16R61)the Special Fund Project for the Central Government to Guide Local Science and Technology Development(2020)。
文摘Mitochondria are the power plants of the cell and play key roles in activating the apoptotic pathway in cancer cells,which are readily susceptible to cytotoxic reactive oxygen species and temperature elevations.Herein,we develop a"nanomissile"that targets mitochondria to enhance tumor treatment effects by facilitating mitochondrial dysfunction and releasing cytochrome C to activate the apoptotic pathway of cancer cells under 650-nm laser irradiation.Porphyringrafted polydopamine nanomaterial(PTPF-MitP)is designed as a nanomissile,with integrated O;-evolving photodynamic therapy and moderate photothermal therapy,which can selectively deliver to the mitochondria through a targeting unit,MitP.The cytotoxicity of PTPF-MitP to human lung tumor cells is twice as high as that of PTPF that does not have mitochondrial targeting units.In addition,it represents a realtime visualization and highly efficient treatment for tumor sites in vivo.This development represents a viable strategy for cancer therapy.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.RS-2023-00208427)a Korea University Grant.This work was also supported by National Cancer Institute(NCI)grant(No.R01CA218659)National Institute of Biomedical Imaging and Bioengineering(NIBIB)grant(No.R01EB026207)。
文摘Ferroptosis offers a novel method for overcoming therapeutic resistance of cancers to conventional cancer treatment regimens.Its effective use as a cancer therapy requires a precisely targeted approach,which can be facilitated by using nanoparticles and nanomedicine,and their use to enhance ferroptosis is indeed a growing area of research.While a few review papers have been published on iron-dependent mechanism and inducers of ferroptosis cancer therapy that partly covers ferroptosis nanoparticles,there is a need for a comprehensive review focusing on the design of magnetic nanoparticles that can typically supply iron ions to promote ferroptosis and simultaneously enable targeted ferroptosis cancer nanomedicine.Furthermore,magnetic nanoparticles can locally induce ferroptosis and combinational ferroptosis with diagnostic magnetic resonance imaging(MRI).The use of remotely controllable magnetic nanocarriers can offer highly effective localized image-guided ferroptosis cancer nanomedicine.Here,recent developments in magnetically manipulable nanocarriers for ferroptosis cancer nanomedicine with medical imaging are summarized.This review also highlights the advantages of current state-of-the-art image-guided ferroptosis cancer nanomedicine.Finally,image guided combinational ferroptosis cancer therapy with conventional apoptosis-based therapy that enables synergistic tumor therapy is discussed for clinical translations.
基金the National Natural Science Foundation of China(No.82172040)。
文摘The injectable self-healing polysaccharide hydrogel was prepared by the formation of Schiff base bonds between aldehyde-modified methylcellulose(MC–CHO)and carboxymethyl chitosan(CMC).The copper sulfide nanoparticles(CuS NPs)and pH-sensitive doxorubicin-loaded zeolitic imidazolate frameworks nanoparticles(DOX@ZIF-8 NPs)were prepared and could be well-dispersed into the hydrogel system.The presence of CuS NPs can achieve photothermal therapy(PTT)for tumors under the irradiation of the near-infrared(NIR)laser.Moreover,CuS NPs can generate photodynamic effects under NIR irradiation,converting oxygen into toxic reactive oxygen species(ROS)and presenting efficient photodynamic therapy(PDT).The DOX@ZIF-8 NPs can be decomposed under an intracellular acidic environment and realize the controlled release of DOX.The injectable self-healing hydrogel loading Cu S and DOX@ZIF-8 NPs can achieve synergistic photothermal-photodynamic-chemo therapy for tumors and will inspire the researchers to construct a platform from hydrogel combined with multifunctional nanomaterials to realize the effective multimodal therapy for tumor.
文摘Multifunctional core-shell nanostructures formed by integration of distinct components have received wide attention as promising biological platforms in recent years. In this work, crystalline zeolitic imidazolate framework-8 （ZIF-8）, a typical metal-organic framework （MOF）, is coated onto single gold nanorod （AuNR） core for successful realization of synergistic photothermal and chemotherapy triggered by near-infrared （NIR） light. Impressivel）~ high doxorubicin hydrochloride （DOX） loading capacity followed by pH and NIR light dual stimuli-responsive DOX release can be easily implemented through formation and breakage of coordination bonds in the system. Moreover, under NIR laser irradiation at 808 nm, these novel AuNR@MOF core-shell nanostructures exhibit effective synergistic chemo-photothermal therapy both in vitro and in vivo, confirmed by cell treatment and tumor ablation via intravenous injection.
基金supported by the National Natural Science Foundation of China(21971153 and 22371172)the Major Basic Research Projects of Shandong Provincial Natural Science Foundation(ZR2020ZD32)+1 种基金Taishan Scholars Climbing Program of Shandong Province,China Postdoctoral Science Foundation(2020M682225)the Natural Science Foundation of Shandong Province(ZR202102280580 and ZR202102210262)。
基金the National Natural Science Foundationof China(Nos.51503200,21474104,5123300451520105004 and 51390484)Jilin Province Science and Technology Development Program(No.20160204032GX)the National Program for Support of Top-notch Young Professionals for financial support
文摘Direct administration of drugs and genes to the lungs by pulmonary delivery offers a potential effective therapy for lung cancers.In this study,combined doxorubicin（DOX） and Bcl2 siRNA was employed for cancer therapy using polyethylenimine（PEI） as the carrier of Bcl2 siRNA.Most of the DOX and siRNA possessed high cellular uptake efficiency in B16F10 cells,which was proved by FCM and CLSM analysis.Real-time PCR showed that PEI/Bcl2 siRNA exhibited high gene silencing efficiency with 70%Bcl2 mRNA being knocked down.The combination of DOX and siRNA could enhance the cell proliferation inhibition and the cell apoptosis against B16F10 cells compared to free DOX or PEI/Bcl2 siRNA.Furthermore,the biodistribution of DOX and siRNA via pulmonary administration was studied in mice with B16F10 metastatic lung cancer.The results showed that most of the DOX and siRNA were accumulated in lungs and lasted at least for 3 days,which suggested that combined DOX and siRNA by pulmonary administration may have high anti-tumor effects for metastatic lung cancer treatment in vivo.
