BACKGROUND： Ultraviolet blood irradiation and oxygenation （UBIO） has obtained better clinical effect in treating acute cerebral infarction, but the mechanism underlying this effect remains unclear. OBJECTIVE： To o...BACKGROUND： Ultraviolet blood irradiation and oxygenation （UBIO） has obtained better clinical effect in treating acute cerebral infarction, but the mechanism underlying this effect remains unclear. OBJECTIVE： To observe the effect of UBIO on the nerve function and activities of K^＋-Na^＋-ATPase and Ca2^＋-Mg2^＋-ATPase activities on the red blood cell （RBC） membrane of patients with acute cerebral infarction. DESIGN： A randomized and controlled study.SETTING： Department of Neurology, Xiangfan Central Hospital.PARTICIPANTS： From January 2000 to December 2001, excluding those above 70 years old, 58 cases of 700 patients with acute cerebral infarction admitted in the Department of Neurology, Xiangfan Central Hospital, were recruited and divided into two groups according to the random number table： UBIO treated group （n=28）, including 17 males and 11 females, aged 40-68 years; and control group （n=30）, including 20 males and 10 females, aged 44-69 years. All the patients agreed to participate in the therapeutic program and detected items. The general informations were comparable without obvious differences between the two groups （P 〉 0.05）.METHODS： ① The patients in both groups received routine treatments, besides, those in the UBIO treated group were given UBIO treatment by using the XL-200 type therapeutic apparatus produced in Shijiazhuang, whose ultraviolet wave was set at 253.7 nm with the energy density of 0.568 J/m^2 per second, UBIO treatment started from the second day after admission, once every other day, with a single course consisting of 5-7 treatments. ② In the UBIO treated group, the venous blood was sampled before and after the first, third and the completion of the treatment course respectively, the venous blood was taken at each corresponding time point in the control group. After centrifugation of the blood at 10 000 rounds per minute, the RBC membrane was separated and then the activities of K^＋-Na^＋-ATPase and Ca2^＋-Mg2^＋-ATPase were detected by means of phosphorus determination.③ The nerve function was scored before and after treatment in both groups with European stroke scale, which included 13 items, the total score was 0-100 points, the higher the score, the better the nerve function. MAIN OUTCOME MEASURES ：①Score of European stroke scale before and after treatment in both groups.② Comparison of the activities of K^＋-Na^＋-ATPase and Ca2^＋-Mg2^＋-ATPase on RBC membrane between the two groups before treatment and after the first, third and the completion of the treatment. RESULTS： All the 58 patients with cerebral infarction were involved in the analysis of results.① The score of European stroke scale had no obvious difference between the two groups [（49.31±11.48）, （50.58±12.63）, P 〉 0.05], and it was obviously higher in the UBIO treated group than in the control group after treatment [84.66±13.75）, （77.05±11.17）, P 〈 0.05].②The activity of K^＋-Na^＋-ATPase on RBC membrane in the UBIO treated group was significantly increased after the first and third treatment as compared with before treatment [（31.56±19.25）, （27.64±15.83）, （17.67±13.83）, P 〈 0.01], it was still higher after the completion of the treatment than before treatment without obvious difference [（20.86±14.53）, P 〉 0.05]. After the first and third treatment, it was obviously higher in the UBIO treated group than in the control group [19.31±11.88）, （17.44±10.42）, P 〈 0.01]. ③ In the UBIO treated group, Ca2^＋-Mg2^＋-ATPase activity on RBC membrane significantly increased after the first treatment and remained higher than the pre-treatment level throughout the treatment [（27.49±14.72）, （17.41±4.82）, P 〈 0.01]. The activity of Ca2^＋-Mg2^＋-ATPase on RBC membrane was markedly higher in the UBIO treated group than in the control group after after the first, third and the completion of treatment respectively [（24.83±12.88）, （17.70±5.69）; （28.08±13.44）, （16.32±5.29）; （17.42±6.04）, P〈 0.05-0.01]. CONCLUSION： The effect of UBIO treatment against acute cerebral infarction may be mediated by the increased K^＋-Na^＋ ATPase and Ca2^＋-Mg2^＋-ATPase activities on RBC membrane, which enhances the RBC transformation ability so as to lower RBC aggregation and correct high blood viscosity.展开更多
FMS-like tyrosine kinase 3(FLT3)is a viable and important therapeutic target for acute myeloid leukemia(AML).FLT3 internal tandem duplication(FLT3-ITD)mutations have been identified in approximately 30%of AML patients...FMS-like tyrosine kinase 3(FLT3)is a viable and important therapeutic target for acute myeloid leukemia(AML).FLT3 internal tandem duplication(FLT3-ITD)mutations have been identified in approximately 30%of AML patients,and are associated with unfavorable prognosis,higher risk of relapse,drug resistance,and poor clinical outcome.Even FLT3 inhibitors have demonstrated promising efficacy,they cannot cure AML or even significantly extend the lives of patients with FLT3-ITD mutations.This is partly because of poor water solubility,insufficient membrane penetration and short half-life of small molecule inhibitors.Besides,the presence of enzymes like CYP3A4 in bone marrow accelerate the elimination and metabolism of FLT3 inhibitors,resulting in low plasma concentrations and side effects.Here we report the erythrocyte membrane-camouflaged FLT3 inhibitor nanoparticles to enhance FLT3-ITD AML treatment.Briefly,we physically coextruded red blood cell(RBC)membrane vesicles with nanoparticles derived from FLT3 inhibitor F30 to obtain F30@RBC-M,which exhibited comparable potent FLT3-ITD inhibitory effects compared to free F30 in vitro,while displaying a higher potent antitumor efficacy in xenograft models due to the prolonged circulation properties.Furthermore,administration of F30@RBC-M significantly extended the survival of mice in a transplanted mouse model than F30 free drug.These findings suggest that RBC membrane-coated nanoparticles derived from FLT3 inhibitors hold promise as a tool to enhance the therapeutic efficacy to treat FLT3-ITD AML.展开更多
In this work, the previously developed coarse-grained （CG） particle models for biomembranes and red blood cells （RBCs） are reviewed, and the advantages of the CG particle methods over the continuum and atomistic s...In this work, the previously developed coarse-grained （CG） particle models for biomembranes and red blood cells （RBCs） are reviewed, and the advantages of the CG particle methods over the continuum and atomistic simulations for modeling biological phenomena are discussed. CG particle models can largely increase the length scale and time scale of atomistic simulations by eliminating the fast degrees of freedom while preserving the mesoscopic structures and properties of the simulated system. Moreover, CG particle models can be used to capture the microstructural alternations in diseased RBCs and simulate the topological changes of biomembranes and RBCs, which are the major challenges to the typical continuum representations of membranes and RBCs. The power and versatility of CG particle methods are demonstrated：through simulating the dynamical processes mvolving significant topological .changes e.g. lipid self-assembly vesicle fusion and membrane budding.展开更多
Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated ...Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated SPNs with sur-face cloaked by red blood cell membrane(RBCM)are developed for highly e ective photoacoustic imaging and photothermal therapy.The resulting RBCM-coated SPN(SPN@RBCM)displays remarkable near-infrared light absorption and good photosta-bility,as well as high photothermal conver-sion e ciency for photoacoustic imaging and photothermal therapy.Particularly,due to the small size(<5 nm),SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity.The RBCM endows the SPNs with prolonged systematic circulation time,less reticuloendothelial system uptake and reduced immune-recognition,hence improving tumor accumulation after intravenous injection,which provides strong photoacoustic signals and exerts excellent photothermal therapeutic e ects.Thus,this work provides a valuable paradigm for safe and highly e cient tumor pho-toacoustic imaging and photothermal therapy for further clinical translation.展开更多
In situ regeneration is a promising strategy for constructing tissue engineering heart valves(TEHVs).Currently,the decellularized heart valve(DHV)is extensively employed as a TEHV scaffold.Nevertheless,DHV exhibits li...In situ regeneration is a promising strategy for constructing tissue engineering heart valves(TEHVs).Currently,the decellularized heart valve(DHV)is extensively employed as a TEHV scaffold.Nevertheless,DHV exhibits limited blood compatibility and notable difficulties in endothelialization,resulting in thrombosis and graft failure.The red blood cell membrane(RBCM)exhibits excellent biocompatibility and prolonged circulation stability and is extensively applied in the camouflage of nanoparticles for drug delivery;however,there is no report on its application for large-scale modification of decellularized extracellular matrix(ECM).For the first time,we utilized a layer-by-layer assembling strategy to immobilize RBCM on the surface of DHV and construct an innovative TEHV scaffold.Our findings demonstrated that the scaffold significantly improved the hemocompatibility of DHV by effectively preventing plasma protein adsorption,activated platelet adhesion,and erythrocyte aggregation,and induced macrophage polarization toward the M2 phenotype in vitro.Moreover,RBCM modification significantly enhanced the mechanical properties and enzymatic stability of DHV.The rat models of subcutaneous embedding and abdominal aorta implantation showed that the scaffold regulated the polarization of macrophages into the anti-inflammatory and pro-modeling M2 phenotype and promoted endothelialization and ECM remodeling in the early stage without thrombosis and calcification.The novel TEHV exhibits excellent performance and can overcome the limitations of commonly used clinical prostheses.展开更多
Objective: To explore the mechanism ofintegrated traditional Chinese and Westernmedicine (TCM--WM ) therapy on chronicaplastic anemia (CAA). Methods: The RBClife span of 30 normal human subjects and 30patients with CA...Objective: To explore the mechanism ofintegrated traditional Chinese and Westernmedicine (TCM--WM ) therapy on chronicaplastic anemia (CAA). Methods: The RBClife span of 30 normal human subjects and 30patients with CAA were measured by sir labelled technique before and after TCM--WMtherapy. The morphology and distribution ofRBC membrane protein granules were observed by freeze fracture etching and transmission electron microscope. Results: The halflife of erythrocytes (RBC TI/2)was shortenedin CAA cases and there was a significant difference compared to healthy control (P <0. 01). After therapy, the RBC life span prolonged and approached the normal level. Before treatment, there existed abnormal in morphology, decrease in amount and uneven indistribution of protein granules in protoplasmicface (PF) and extracellular face (EF) of RBCmembrane. After treatment, the protein granules of RBC membrane was improved and approached to control. Conclusions: The morphology, amount, quality and distribution ofRBC membrane protein granule were closelyrelated to its life span. The therapeutic effectof TCM--WM was better than that of WMalone and it had a function both in stabilizingmembrane protein and extending the RBC lifespan.展开更多
The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics.Bacterial infections are detrimental to our life ...The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics.Bacterial infections are detrimental to our life and health.To reduce the abuse of antibiotics and treat biofilm-related bacterial infections,a biomimetic nano-antibacterial system,RBCM-NW-G namely,that controls the release of antibiotics through near infrared was prepared.The hollow porous structure and the high surface activity of nanoworms are used to realize antibiotic loading,and then,biomimetics are applied with red blood cell membranes(RBCM).RBCM-NW-G,which retains the performance of RBCM,shows enhanced permeability and retention effects.Fluorescence imaging in mice showed the effective accumulation of RBCM-NW-G at the site of infection.In addition,the biomimetic nanoparticles showed a longer blood circulation time and good biocompatibility.Anti-biofilm test results showed damage to biofilms due to a photothermal effect and a highly efficient antibacterial performance under the synergy of the photothermal effect,silver iron,and antibiotics.Finally,by constructing a mouse infection model,the great potential of RBCM-NW-G in the treatment of in vivo infections was confirmed.展开更多
Combining photothermal therapy and radiotherapy(PTT-RT) with reducing tumor hypoxia acts as an important antitumor modality. However, it is a great challenge to realize photothermal therapy, radiotherapy and exogenous...Combining photothermal therapy and radiotherapy(PTT-RT) with reducing tumor hypoxia acts as an important antitumor modality. However, it is a great challenge to realize photothermal therapy, radiotherapy and exogenous oxygen supply in one nanosystem. To realize a combination of the three functions, we fabricated a red blood cell membrane(RBCm)-camouflaged, red blood cell content(RBCc) and the copper sulfide(CuS) co-loaded dendritic large pore mesoporous silica nanoparticle(DLMSN/CuS/RBCc/ RBCm). The cell membrane coating endowed the nanoparticles with good stability in the physiological environment, and CuS allowed the nanoparticle exhibiting good photothermal and radiosensitization properties. RBCc loaded nanoparticle DLMSN/CuS/RBCc enhanced superior anti-tumor effect than DLMSN/CuS during combined PTT-RT therapy because the introduction of RBCc increased the exogenous oxygen supply. The in vitro study further demonstrated that the combination of photothermal therapy and radiotherapy induced superior antitumor efficacy than single therapy. Our work thus presents a unique multifunctional nanoscale platform favorable for combined PTT and RT.展开更多
MicroRNA-208a(miR-208a)plays critical roles in the severe fibrosis and heart failure post myocardial ischemia/reperfusion(IR)injury.MiR-208a inhibitor(mI)with complementary RNA sequence can silence the expression of m...MicroRNA-208a(miR-208a)plays critical roles in the severe fibrosis and heart failure post myocardial ischemia/reperfusion(IR)injury.MiR-208a inhibitor(mI)with complementary RNA sequence can silence the expression of miR-208a,while it is challenging to achieve efficient and myocardium-targeted delivery.Herein,biomimetic nanocomplexes(NCs)reversibly coated with red blood cell membrane(RM)were developed for the myocardial delivery of mI.To construct the NCs,membrane-penetrating helical polypeptide(PG)was first adopted to condense mI and form the cationic inner core,which subsequently adsorbed catalase(CAT)via electrostatic interaction followed by surface coating with RM.The membrane-coated NCs enabled prolonged blood circulation after systemic administration,and could accumulate in the injured myocardium via passive targeting.In the oxidative microenvironment of injured myocardium,CAT decomposed H_(2)O_(2)to produce O_(2)bubbles,which drove the shedding of the outer RM to expose the positively charged inner core,thus facilitated effective internalization by cardiac cells.Based on the combined contribution of mI-mediated miR-208a silencing and CAT-mediated alleviation of oxidative stress,NCs effectively ameliorated the myocardial microenvironment,hence reducing the infarct size as well as fibrosis and promoting recovery of cardiac functions.This study provides an effective strategy for the cytosolic delivery of nucleic acid cargoes in the myocardium,and it renders an enlightened approach to resolve the blood circulation/cell internalization dilemma of cell membrane-coated delivery systems.展开更多
Bacteria-related wound infection and healing have been a major issue for patients and health-care systems for decades.The rise and evolution of effective treatment will result in significant benefits to human beings.I...Bacteria-related wound infection and healing have been a major issue for patients and health-care systems for decades.The rise and evolution of effective treatment will result in significant benefits to human beings.In ad-dition to standard antibacterial drugs,a combination of nanoparticles(NPs)and biological membranes is widely applied as a novel antibacterial agent against infectious pathogens.In this paper,the red blood cell membrane-encapsulated selenium nanoparticles(R-SeNPs)were fabricated for infectious wound healing.The stability,the immune evading capability,and the internal circulation time of the R-SeNPs were notably enhanced compared with those of bare selenium nanoparticles(SeNPs).Moreover,in vivo studies demonstrated the outstanding per-formance of the R-SeNPs in infectious wound healing.The biomimetic selenium nanosystem demonstrated the benefits of the combination of nanotechnology and bionics design and will contribute to wound healing in the future.展开更多
Anti virulence strategy has been considered as one of the most promising approaches to combat drug-rcesistant bacterial infections.Porc-forming toxins(PFTs)are the largest class of bacterial toxins,inficting their vir...Anti virulence strategy has been considered as one of the most promising approaches to combat drug-rcesistant bacterial infections.Porc-forming toxins(PFTs)are the largest class of bacterial toxins,inficting their virulence ffect through creating pores on the cell membrane.However,curent solutions for eliminating PFTs are mostly designed based on their molecular structure,requiring customized design for different interactions.In the present study,we employed erythroliposome(denoted as RM-PL),a biomimetic platform constructed by artificial lipid membranes and natural erythrocyle membranes,to necutralize different hemolytic PFTs regardless of their molecular structure.When tested with model PFTs,including a-hemolysin,listeriolysin O,and streptolysin O,RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner.In vivo studies further confirmed that RM-PL.could eficiently neuralize various toxins and save animals'lives without causing damage to 0rgans or tissues.In addition,we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes.In summary,the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mech-anism of lysosome-mediaed loxin degradation.展开更多
文摘BACKGROUND： Ultraviolet blood irradiation and oxygenation （UBIO） has obtained better clinical effect in treating acute cerebral infarction, but the mechanism underlying this effect remains unclear. OBJECTIVE： To observe the effect of UBIO on the nerve function and activities of K^＋-Na^＋-ATPase and Ca2^＋-Mg2^＋-ATPase activities on the red blood cell （RBC） membrane of patients with acute cerebral infarction. DESIGN： A randomized and controlled study.SETTING： Department of Neurology, Xiangfan Central Hospital.PARTICIPANTS： From January 2000 to December 2001, excluding those above 70 years old, 58 cases of 700 patients with acute cerebral infarction admitted in the Department of Neurology, Xiangfan Central Hospital, were recruited and divided into two groups according to the random number table： UBIO treated group （n=28）, including 17 males and 11 females, aged 40-68 years; and control group （n=30）, including 20 males and 10 females, aged 44-69 years. All the patients agreed to participate in the therapeutic program and detected items. The general informations were comparable without obvious differences between the two groups （P 〉 0.05）.METHODS： ① The patients in both groups received routine treatments, besides, those in the UBIO treated group were given UBIO treatment by using the XL-200 type therapeutic apparatus produced in Shijiazhuang, whose ultraviolet wave was set at 253.7 nm with the energy density of 0.568 J/m^2 per second, UBIO treatment started from the second day after admission, once every other day, with a single course consisting of 5-7 treatments. ② In the UBIO treated group, the venous blood was sampled before and after the first, third and the completion of the treatment course respectively, the venous blood was taken at each corresponding time point in the control group. After centrifugation of the blood at 10 000 rounds per minute, the RBC membrane was separated and then the activities of K^＋-Na^＋-ATPase and Ca2^＋-Mg2^＋-ATPase were detected by means of phosphorus determination.③ The nerve function was scored before and after treatment in both groups with European stroke scale, which included 13 items, the total score was 0-100 points, the higher the score, the better the nerve function. MAIN OUTCOME MEASURES ：①Score of European stroke scale before and after treatment in both groups.② Comparison of the activities of K^＋-Na^＋-ATPase and Ca2^＋-Mg2^＋-ATPase on RBC membrane between the two groups before treatment and after the first, third and the completion of the treatment. RESULTS： All the 58 patients with cerebral infarction were involved in the analysis of results.① The score of European stroke scale had no obvious difference between the two groups [（49.31±11.48）, （50.58±12.63）, P 〉 0.05], and it was obviously higher in the UBIO treated group than in the control group after treatment [84.66±13.75）, （77.05±11.17）, P 〈 0.05].②The activity of K^＋-Na^＋-ATPase on RBC membrane in the UBIO treated group was significantly increased after the first and third treatment as compared with before treatment [（31.56±19.25）, （27.64±15.83）, （17.67±13.83）, P 〈 0.01], it was still higher after the completion of the treatment than before treatment without obvious difference [（20.86±14.53）, P 〉 0.05]. After the first and third treatment, it was obviously higher in the UBIO treated group than in the control group [19.31±11.88）, （17.44±10.42）, P 〈 0.01]. ③ In the UBIO treated group, Ca2^＋-Mg2^＋-ATPase activity on RBC membrane significantly increased after the first treatment and remained higher than the pre-treatment level throughout the treatment [（27.49±14.72）, （17.41±4.82）, P 〈 0.01]. The activity of Ca2^＋-Mg2^＋-ATPase on RBC membrane was markedly higher in the UBIO treated group than in the control group after after the first, third and the completion of treatment respectively [（24.83±12.88）, （17.70±5.69）; （28.08±13.44）, （16.32±5.29）; （17.42±6.04）, P〈 0.05-0.01]. CONCLUSION： The effect of UBIO treatment against acute cerebral infarction may be mediated by the increased K^＋-Na^＋ ATPase and Ca2^＋-Mg2^＋-ATPase activities on RBC membrane, which enhances the RBC transformation ability so as to lower RBC aggregation and correct high blood viscosity.
基金supported by the National Natural Science Foundation of China(No.32222046,China)the Sichuan Science and Technology Program(Nos.2022NSFSC0823,2023NSFSC193,2022NSFSC0793,China)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21022,China).
文摘FMS-like tyrosine kinase 3(FLT3)is a viable and important therapeutic target for acute myeloid leukemia(AML).FLT3 internal tandem duplication(FLT3-ITD)mutations have been identified in approximately 30%of AML patients,and are associated with unfavorable prognosis,higher risk of relapse,drug resistance,and poor clinical outcome.Even FLT3 inhibitors have demonstrated promising efficacy,they cannot cure AML or even significantly extend the lives of patients with FLT3-ITD mutations.This is partly because of poor water solubility,insufficient membrane penetration and short half-life of small molecule inhibitors.Besides,the presence of enzymes like CYP3A4 in bone marrow accelerate the elimination and metabolism of FLT3 inhibitors,resulting in low plasma concentrations and side effects.Here we report the erythrocyte membrane-camouflaged FLT3 inhibitor nanoparticles to enhance FLT3-ITD AML treatment.Briefly,we physically coextruded red blood cell(RBC)membrane vesicles with nanoparticles derived from FLT3 inhibitor F30 to obtain F30@RBC-M,which exhibited comparable potent FLT3-ITD inhibitory effects compared to free F30 in vitro,while displaying a higher potent antitumor efficacy in xenograft models due to the prolonged circulation properties.Furthermore,administration of F30@RBC-M significantly extended the survival of mice in a transplanted mouse model than F30 free drug.These findings suggest that RBC membrane-coated nanoparticles derived from FLT3 inhibitors hold promise as a tool to enhance the therapeutic efficacy to treat FLT3-ITD AML.
基金Project supported by the National Institutes of Health of U.S.A.(No.U01HL114476)the National Science Foundation of U.S.A.(Nos.CMMI-1235025 and PHY-1205910)
文摘In this work, the previously developed coarse-grained （CG） particle models for biomembranes and red blood cells （RBCs） are reviewed, and the advantages of the CG particle methods over the continuum and atomistic simulations for modeling biological phenomena are discussed. CG particle models can largely increase the length scale and time scale of atomistic simulations by eliminating the fast degrees of freedom while preserving the mesoscopic structures and properties of the simulated system. Moreover, CG particle models can be used to capture the microstructural alternations in diseased RBCs and simulate the topological changes of biomembranes and RBCs, which are the major challenges to the typical continuum representations of membranes and RBCs. The power and versatility of CG particle methods are demonstrated：through simulating the dynamical processes mvolving significant topological .changes e.g. lipid self-assembly vesicle fusion and membrane budding.
基金supported by the National Natural Science Foundation of China(Grant Nos.61727823,51873160)the joint research project of Health and Education Commission of Fujian Province(Grant No.2019-WJ-20).
文摘Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated SPNs with sur-face cloaked by red blood cell membrane(RBCM)are developed for highly e ective photoacoustic imaging and photothermal therapy.The resulting RBCM-coated SPN(SPN@RBCM)displays remarkable near-infrared light absorption and good photosta-bility,as well as high photothermal conver-sion e ciency for photoacoustic imaging and photothermal therapy.Particularly,due to the small size(<5 nm),SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity.The RBCM endows the SPNs with prolonged systematic circulation time,less reticuloendothelial system uptake and reduced immune-recognition,hence improving tumor accumulation after intravenous injection,which provides strong photoacoustic signals and exerts excellent photothermal therapeutic e ects.Thus,this work provides a valuable paradigm for safe and highly e cient tumor pho-toacoustic imaging and photothermal therapy for further clinical translation.
基金supported by the National Key Research and Development Program of China(2021YFA1101900 and 2023YFB3810100)the National Natural Science Foundation of China(82270381 and 81930052)the Major Science and Technology Special Plan Project of Yunnan Province(202302AA310045).
文摘In situ regeneration is a promising strategy for constructing tissue engineering heart valves(TEHVs).Currently,the decellularized heart valve(DHV)is extensively employed as a TEHV scaffold.Nevertheless,DHV exhibits limited blood compatibility and notable difficulties in endothelialization,resulting in thrombosis and graft failure.The red blood cell membrane(RBCM)exhibits excellent biocompatibility and prolonged circulation stability and is extensively applied in the camouflage of nanoparticles for drug delivery;however,there is no report on its application for large-scale modification of decellularized extracellular matrix(ECM).For the first time,we utilized a layer-by-layer assembling strategy to immobilize RBCM on the surface of DHV and construct an innovative TEHV scaffold.Our findings demonstrated that the scaffold significantly improved the hemocompatibility of DHV by effectively preventing plasma protein adsorption,activated platelet adhesion,and erythrocyte aggregation,and induced macrophage polarization toward the M2 phenotype in vitro.Moreover,RBCM modification significantly enhanced the mechanical properties and enzymatic stability of DHV.The rat models of subcutaneous embedding and abdominal aorta implantation showed that the scaffold regulated the polarization of macrophages into the anti-inflammatory and pro-modeling M2 phenotype and promoted endothelialization and ECM remodeling in the early stage without thrombosis and calcification.The novel TEHV exhibits excellent performance and can overcome the limitations of commonly used clinical prostheses.
文摘Objective: To explore the mechanism ofintegrated traditional Chinese and Westernmedicine (TCM--WM ) therapy on chronicaplastic anemia (CAA). Methods: The RBClife span of 30 normal human subjects and 30patients with CAA were measured by sir labelled technique before and after TCM--WMtherapy. The morphology and distribution ofRBC membrane protein granules were observed by freeze fracture etching and transmission electron microscope. Results: The halflife of erythrocytes (RBC TI/2)was shortenedin CAA cases and there was a significant difference compared to healthy control (P <0. 01). After therapy, the RBC life span prolonged and approached the normal level. Before treatment, there existed abnormal in morphology, decrease in amount and uneven indistribution of protein granules in protoplasmicface (PF) and extracellular face (EF) of RBCmembrane. After treatment, the protein granules of RBC membrane was improved and approached to control. Conclusions: The morphology, amount, quality and distribution ofRBC membrane protein granule were closelyrelated to its life span. The therapeutic effectof TCM--WM was better than that of WMalone and it had a function both in stabilizingmembrane protein and extending the RBC lifespan.
基金This work was supported by the National Natural Science Foundation of China(Nos.51803170,51803171 and 81703424)China Agricultural Research System(No.CARS-18-ZJ0102)Fundamental Research Funds for the Central Universities(2020CDJQY-A041).
文摘The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics.Bacterial infections are detrimental to our life and health.To reduce the abuse of antibiotics and treat biofilm-related bacterial infections,a biomimetic nano-antibacterial system,RBCM-NW-G namely,that controls the release of antibiotics through near infrared was prepared.The hollow porous structure and the high surface activity of nanoworms are used to realize antibiotic loading,and then,biomimetics are applied with red blood cell membranes(RBCM).RBCM-NW-G,which retains the performance of RBCM,shows enhanced permeability and retention effects.Fluorescence imaging in mice showed the effective accumulation of RBCM-NW-G at the site of infection.In addition,the biomimetic nanoparticles showed a longer blood circulation time and good biocompatibility.Anti-biofilm test results showed damage to biofilms due to a photothermal effect and a highly efficient antibacterial performance under the synergy of the photothermal effect,silver iron,and antibiotics.Finally,by constructing a mouse infection model,the great potential of RBCM-NW-G in the treatment of in vivo infections was confirmed.
基金supported by the National Natural Science Foundation of China(No.12074284)the Natural Science Foundation of Tianjin City,China(No.20JCYBJC00170).
文摘Combining photothermal therapy and radiotherapy(PTT-RT) with reducing tumor hypoxia acts as an important antitumor modality. However, it is a great challenge to realize photothermal therapy, radiotherapy and exogenous oxygen supply in one nanosystem. To realize a combination of the three functions, we fabricated a red blood cell membrane(RBCm)-camouflaged, red blood cell content(RBCc) and the copper sulfide(CuS) co-loaded dendritic large pore mesoporous silica nanoparticle(DLMSN/CuS/RBCc/ RBCm). The cell membrane coating endowed the nanoparticles with good stability in the physiological environment, and CuS allowed the nanoparticle exhibiting good photothermal and radiosensitization properties. RBCc loaded nanoparticle DLMSN/CuS/RBCc enhanced superior anti-tumor effect than DLMSN/CuS during combined PTT-RT therapy because the introduction of RBCc increased the exogenous oxygen supply. The in vitro study further demonstrated that the combination of photothermal therapy and radiotherapy induced superior antitumor efficacy than single therapy. Our work thus presents a unique multifunctional nanoscale platform favorable for combined PTT and RT.
基金supported by the National Natural Science Foundation of China(Nos.82172076,52273144,and 52033006)111 project,Collaborative Innovation Center of Suzhou Nano Science&Technology,Joint International Research Laboratory of Carbon-Based Functional Materials and Devices,and Suzhou Key Laboratory of Nanotechnology and Biomedicine.
文摘MicroRNA-208a(miR-208a)plays critical roles in the severe fibrosis and heart failure post myocardial ischemia/reperfusion(IR)injury.MiR-208a inhibitor(mI)with complementary RNA sequence can silence the expression of miR-208a,while it is challenging to achieve efficient and myocardium-targeted delivery.Herein,biomimetic nanocomplexes(NCs)reversibly coated with red blood cell membrane(RM)were developed for the myocardial delivery of mI.To construct the NCs,membrane-penetrating helical polypeptide(PG)was first adopted to condense mI and form the cationic inner core,which subsequently adsorbed catalase(CAT)via electrostatic interaction followed by surface coating with RM.The membrane-coated NCs enabled prolonged blood circulation after systemic administration,and could accumulate in the injured myocardium via passive targeting.In the oxidative microenvironment of injured myocardium,CAT decomposed H_(2)O_(2)to produce O_(2)bubbles,which drove the shedding of the outer RM to expose the positively charged inner core,thus facilitated effective internalization by cardiac cells.Based on the combined contribution of mI-mediated miR-208a silencing and CAT-mediated alleviation of oxidative stress,NCs effectively ameliorated the myocardial microenvironment,hence reducing the infarct size as well as fibrosis and promoting recovery of cardiac functions.This study provides an effective strategy for the cytosolic delivery of nucleic acid cargoes in the myocardium,and it renders an enlightened approach to resolve the blood circulation/cell internalization dilemma of cell membrane-coated delivery systems.
基金This work was supported by the National Natural Science Foundation of China(82170224 and 82102511)the Natural Science Foundation of Jiangsu(BK20210021)Research Project of Jiangsu Province Health Committee(H2019081).
文摘Bacteria-related wound infection and healing have been a major issue for patients and health-care systems for decades.The rise and evolution of effective treatment will result in significant benefits to human beings.In ad-dition to standard antibacterial drugs,a combination of nanoparticles(NPs)and biological membranes is widely applied as a novel antibacterial agent against infectious pathogens.In this paper,the red blood cell membrane-encapsulated selenium nanoparticles(R-SeNPs)were fabricated for infectious wound healing.The stability,the immune evading capability,and the internal circulation time of the R-SeNPs were notably enhanced compared with those of bare selenium nanoparticles(SeNPs).Moreover,in vivo studies demonstrated the outstanding per-formance of the R-SeNPs in infectious wound healing.The biomimetic selenium nanosystem demonstrated the benefits of the combination of nanotechnology and bionics design and will contribute to wound healing in the future.
基金supported by the National Natural Science Foundation of China(81773283).
文摘Anti virulence strategy has been considered as one of the most promising approaches to combat drug-rcesistant bacterial infections.Porc-forming toxins(PFTs)are the largest class of bacterial toxins,inficting their virulence ffect through creating pores on the cell membrane.However,curent solutions for eliminating PFTs are mostly designed based on their molecular structure,requiring customized design for different interactions.In the present study,we employed erythroliposome(denoted as RM-PL),a biomimetic platform constructed by artificial lipid membranes and natural erythrocyle membranes,to necutralize different hemolytic PFTs regardless of their molecular structure.When tested with model PFTs,including a-hemolysin,listeriolysin O,and streptolysin O,RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner.In vivo studies further confirmed that RM-PL.could eficiently neuralize various toxins and save animals'lives without causing damage to 0rgans or tissues.In addition,we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes.In summary,the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mech-anism of lysosome-mediaed loxin degradation.
