The escalation in the incidence of multidrug-resistant Gram-negative bacteria is becoming a pressing global concern.Polymyxin B(PMB),a conventional antibiotic with notable therapeutic efficacy against Gram-negative ba...The escalation in the incidence of multidrug-resistant Gram-negative bacteria is becoming a pressing global concern.Polymyxin B(PMB),a conventional antibiotic with notable therapeutic efficacy against Gram-negative bacterial infections,serves as a crucial final recourse against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Nevertheless,the clinical usage of PMB is impeded by its pronounced nephrotoxicity and poor infection site targeting.This investigation is geared to construct a nanoparticle formulation(named HA-PMB@H)comprising hyaluronic acid(HA)and PMB via a simple Schiff base reaction and further coating HA by electrostatic action.HA-PMB@H shows an average size of(153.8±24.3)nm,and a mean zeta potential of(−25.6±5.2)mV.Additionally,PMB can be released from HA-PMB@H more thoroughly and efficiently at pH 5.5 compared to pH 7.4,which demonstrates the Schiff base modification of PMB paves the way for its release at focus of infection.The uptake ratio of HA-PMB@H by alveolar epithelial cells(RLE-6TN)surpassed that of free PMB devoid of HA,which facilitates to the intracellular sterilization of PMB.Furthermore,the employment of HA-PMB@H ameliorated the toxicity of PMB towards human embryonic kidney cells(HEK 293)and pulmonary microvascular endothelial cells(HULEC-5a).What is more,HA-PMB@H effectively managed severe pneumonia induced by CRKP samples from clinical patients diagnosed with CRKP infection in vivo,substantially enhancing the survival rate of mice.Consequently,this nano-delivery system holds promising clinical significance in the combat against drug-resistant bacterial infections.展开更多
Oral tyrosine kinase inhibitors(TKIs) against epidermal growth factor receptor(EGFR) family have been introduced into the clinic to treat human malignancies for decades. Despite superior properties of EGFR-TKIs as sma...Oral tyrosine kinase inhibitors(TKIs) against epidermal growth factor receptor(EGFR) family have been introduced into the clinic to treat human malignancies for decades. Despite superior properties of EGFR-TKIs as small molecule targeted drugs, their applications are still restricted due to their low solubility, capricious oral bioavailability, large requirement of daily dose, high binding tendency to plasma albumin and initial/acquired drug resistance. Nanotechnology is a promising tool to improve efficacy of these drugs. Through non-oral routes. Various nanotechnology-based delivery approaches have been developed for providing efficient delivery of EGFR-TKIs with a better pharmacokinetic profile and tissue-targeting ability. This review aims to indicate the advantage of nanocarriers for EGFR-TKIs delivery.展开更多
Photodynamic therapy(PDT)brings new hope for the treatment of breast cancer due to few side effects and highly effective cell killing;however,the low bioavailability of traditional photosensitizers(PSs)and their depen...Photodynamic therapy(PDT)brings new hope for the treatment of breast cancer due to few side effects and highly effective cell killing;however,the low bioavailability of traditional photosensitizers(PSs)and their dependence on oxygen severely limits their application.Aggregation-induced emission(AIE)PSs can dramatically facilitate the photosensitization effect,which can have positive impacts on tumor PDT.To-date,most AIE PSs lack tumor targeting capability and possess poor cell delivery,resulting in their use in large quantities that are harmful to healthy tissues.In this study,a series of AIE PSs based on pyridinium-substituted triphenylamine salts(TTPAs 1-6)with different alkyl chain lengths are synthesized.Results reveal that TTPAs 1-6 promote the generation of type I and II ROS,including·OH and 1O_(2).In particular,the membrane permeability and targeting of TTPAs 4-6 bearing C8-C10 side-chains are higher than TTPAs 1-3 bearing shorter alkyl chains.Additionally,they can assemble with albumin,thereby forming nanoparticles(TTPA 4-6 NPs)in situ in blood,which significantly facilitates mitochondrial-targeting and strong ROS generation ability.Moreover,the TTPA 4-6 NPs are pH-responsive,allowing for increased accumulation or endocytosis of the tumor and enhancing the imaging or therapeutic effect.Therefore,the in vivo distributions of TTPA 4-6 NPs are visually enriched in tumor sites and exhibited excellent PDT efficacy.This work demonstrates a novel strategy for AIE PDT and has the potential to play an essential role in clinical applications using nano-delivery systems.展开更多
The prevalence of skin cancer is rising along with the rapid population aging in recent years.Traditional therapies,such as surgical treatment,radiotherapy,chemotherapy,photodynamic therapy,and immunotherapy,may accom...The prevalence of skin cancer is rising along with the rapid population aging in recent years.Traditional therapies,such as surgical treatment,radiotherapy,chemotherapy,photodynamic therapy,and immunotherapy,may accompany serious side effects,limiting their clinical benefits.According to the biological characteristics of skin cancer,we have already established two kinds of synergetic systems of photothermal therapy(microneedle)and chemotherapy,containing gold nanorods(GNR).Although the microneedle system exhibited great potential for skin cancer treatment,the system could be still improved further.So,we designed a near-infrared lightresponsive 5-fluorouracil(5-Fu)and indocyanine green(ICG)loaded monomethoxy-poly(ethylene glycol)-polycaprolactone(MPEG-PCL)nanoparticle(5-Fu-ICG-MPEG-PCL),and then 5-Fu-ICG-MPEG-PCL was integrated with a hyaluronic acid dissolvable microneedle system(HA MN)to get 5-Fu-ICG-MPEG-PCL loaded HA MN for treating skin cancers,including human epidermoid cancer and melanoma.In this system,hyaluronic acid,the microneedle carrier,possesses good skin penetration ability and is approved by FDA as a pharmaceutical adjuvant;5-Fu is recommended by FDA for skin cancer treatment;ICG,a photothermal agent,possesses a strong photothermal ability and is approved by FDA for its use in the human body.We hypothesized that 5-Fu-ICG-MPEG-PCL could be delivered by the dissolvable microneedle through the skin,and the release behavior of the drug in the nanoparticle could be controlled by near-infrared light for achieving a single-dose cure of skin cancer,improving the cure rate of skin cancer and providing a new idea and possibility for the clinical treatment of skin cancer.展开更多
Breast cancer has become the most commonly diagnosed cancer type in the world.A combination of chemotherapy and photothermal therapy(PTT) has emerged as a promising strategy for breast cancer therapy.However,the intri...Breast cancer has become the most commonly diagnosed cancer type in the world.A combination of chemotherapy and photothermal therapy(PTT) has emerged as a promising strategy for breast cancer therapy.However,the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle.Therefore,to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect,a multifunctional nanoparticle system(PCRHNs) is developed,which is grafted onto the prussian blue nanoparticles(PB NPs) by reductionresponsive camptothecin(CPT) prodrug copolymer,and then modified with tumor-targeting peptide cyclo(Asp-D-Phe-Lys-Arg-Gly)(cRGD) and hyaluronic acid(HA).PCRHNs exhibited nano-sized structure with good monodispersity,high load efficiency of CPT,triggered CPT release in response to reduction environment,and excellent photothermal conversion under laser irradiation.Furthermore,PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT.In vivo studies indicate that PCRHNs exhibited excellent bio compatibility,prolonged blood circulation,enhanced tumor accumulation,allow tumor-specific che mo-photo thermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity.Moreover,hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT.Collectively,PCRHNs may be a promising therapeutic way for breast cancer therapy.展开更多
mproving the eficacy of melanoma treatment remains an important global challenge.Here,we combined chemotherapy with protein tyrosine phosphatase nonreceptor type 2(Ptpn2)based immunotherapy in an effort to address thi...mproving the eficacy of melanoma treatment remains an important global challenge.Here,we combined chemotherapy with protein tyrosine phosphatase nonreceptor type 2(Ptpn2)based immunotherapy in an effort to address this challenge.Shorthairpin RNA(shRNA)targeting Ptpn2 was coencapsulated with doxorubicin(DOX)in the cell membrane of MI macrophages(MIHD@RPR).The prepared nanoparticles(NPs)were effectively phagocytosed by B16F10 cells and MI macrophages,but not by MOmacrophages.Hence,NPevasion from the reticuloendothelial system(RES)was improved and NPenrichment in tumor sites increased.MIHD@RPR can directly kill tumor cells and stimulate immunogenic cell death(ICD)by DOX and downregulate Ptpn2.It can promote Ml macrophage polarization and dendritic cell maturation and increase the proportion of CD8+T cells.MIHD@RPR killed and inhibited the growth of primary melanoma and lung metastatic tumor celis without harming the surrounding tssue.These findings establish MIHD@RPR as a safe multifunctional nanoparticle capable of effectively combining chemotherapy and gene immunotherapies against melanoma.展开更多
In recent years,Non-Hodgkin lymphoma(NHL)has been one of the most fast-growing malignant tumor diseases.NHL poses severe damages to physical health and a heavy burden to patients.Traditional therapies(chemotherapy or ...In recent years,Non-Hodgkin lymphoma(NHL)has been one of the most fast-growing malignant tumor diseases.NHL poses severe damages to physical health and a heavy burden to patients.Traditional therapies(chemotherapy or radiotherapy)bring some benefit to patients,but have severe adverse effects and do not prevent relapse.The relevance of emerging immunotherapy options(immune-checkpoint blockers or adoptive cellular methods)for NHL remains uncertain,and more intensive evaluations are needed.In this work,inspired by the idea of vaccination to promote an immune response to destroy tumors,we used a biomaterial-based strategy to improve a tumor cell-based vaccine and constructed a novel vaccine named Man-EG7/CH@CpG with antitumor properties.In this vaccine,natural tumor cells are used as a vector to load CpG-ODN,and following lethal irradiation,the formulations were decorated with mannose.The study of the characterization of the doubleimproved vaccine evidenced the enhanced ability of DCs targeting and improved immunocompetence,which displayed an antitumor function.In the lymphoma prevention model,the Man-EG7/CH@CpG vaccine restrained tumor formation with high efficiency.Furthermore,unlike the non-improved vaccine,the double-improved vaccine elicited an enhanced antitumor effect in the lymphoma treatment model.Next,to improve the moderate therapeutic effect of the mono-treatment method,we incorporated a chemotherapeutic drug(doxorubicin,DOX)into the process of vaccination and devised a combination regimen.Fortunately,a tumor inhibition rate of~85%was achieved via the combination therapy,which could not be achieved by mono-chemotherapy or mono-immunotherapy.In summary,the strategy presented here may provide a novel direction in the establishment of a tumor vaccine and is the basis for a prioritization scheme of immuno-chemotherapy in enhancing the therapeutic effect on NHL.展开更多
This is an erratum to our published paper,the scale bar in Fig.6A was wrong[1].In the paper mentioned above,the scale bar in Fig.6A was wrong[1].We missed a decimal point of the scale bar.The correct scale bar of 5-Fu...This is an erratum to our published paper,the scale bar in Fig.6A was wrong[1].In the paper mentioned above,the scale bar in Fig.6A was wrong[1].We missed a decimal point of the scale bar.The correct scale bar of 5-Fu-ICG-MPEG-PCL@HA MN should be 1.00 mm instead of 100 mm.We have corrected the scale bar in Fig.6 as follows.展开更多
This is an erratum to our published paper,the scale bar in Fig.6A was wrong[1].Erratum In the paper mentioned above, the scale bar in Fig. 6A was wrong [1]. We missed a decimal point of the scale bar. The correct scal...This is an erratum to our published paper,the scale bar in Fig.6A was wrong[1].Erratum In the paper mentioned above, the scale bar in Fig. 6A was wrong [1]. We missed a decimal point of the scale bar. The correct scale bar of 5-Fu-ICG-MPEG-PCL@HA MN should be 1.00 mm instead of 100 mm. We have corrected the scale bar in Fig. 6 as follows.展开更多
Abstract This is an erratum to our published paper,the scale bar in Fig.6A was wrong[1].Erratum In the paper mentioned above,the scale bar in Fig.6A was wrong[1].We missed a decimal point of the scale bar.The correct ...Abstract This is an erratum to our published paper,the scale bar in Fig.6A was wrong[1].Erratum In the paper mentioned above,the scale bar in Fig.6A was wrong[1].We missed a decimal point of the scale bar.The correct scale bar of 5-Fu-ICG-MPEG-PCL@HA MN should be 1.00 mm instead of 100 mm.We have corrected the scale bar in Fig.6 as follows.展开更多
was wrong[1].Erratum In the paper mentioned above,the scale bar in Fig.6A was wrong[1].We missed a decimal point of the scale bar.The correct scale bar of 5-Fu-ICG-MPEG-PCL@HA MN should be 1.00 mm instead of 100 mm.We...was wrong[1].Erratum In the paper mentioned above,the scale bar in Fig.6A was wrong[1].We missed a decimal point of the scale bar.The correct scale bar of 5-Fu-ICG-MPEG-PCL@HA MN should be 1.00 mm instead of 100 mm.We have corrected the scale bar in Fig.6 as follows.展开更多
Abstract This is an erratum to our published paper,the scale bar in Fig.6A was wrong[1].Erratum In the paper mentioned above,the scale bar in Fig.6A was wrong[1].We missed a decimal point of the scale bar.The correct ...Abstract This is an erratum to our published paper,the scale bar in Fig.6A was wrong[1].Erratum In the paper mentioned above,the scale bar in Fig.6A was wrong[1].We missed a decimal point of the scale bar.The correct scale bar of 5-Fu-ICG-MPEG-PCL@HA MN should be 1.00 mm instead of 100 mm.We have corrected the scale bar in Fig.6 as follows.展开更多
Nanotechnology has become the most promising domain to boost the efficiency of enzymes.Enzymes are vital as a green catalyst in many industries,food,pharmaceutical and biomedical,etc.The immobilization process of the ...Nanotechnology has become the most promising domain to boost the efficiency of enzymes.Enzymes are vital as a green catalyst in many industries,food,pharmaceutical and biomedical,etc.The immobilization process of the enzyme increases its catalytic properties.In this research,a novel method is presented to describe the effect of nano-calcium carbonate on the characteristics of immobilizedβ-glucosidase,which was extracted from the Agrocybe aegirit.The nano-CaCO_(3)was produced using the eco-friendly natural deep eutectic solvent.The pure nano-CaCO_(3)was observed as vaterite,with a size of about 300 nm.The nano-calcium carbonate was coated by a natural polymer sodium alginate compound and then adsorbed chitosan.Further,this obtained composite is cross-linked by the bioactive genipin to immobilize theβ-glucosidase.The enzyme/protein loading ratio to the supports was 1:4,respectively.The recovery efficiency of immobilizedβ-glucosidase was 89.3%,and immobilization yield was 96.452%.Chitosan-coated nano-CaCO_(3)was used as a carrier for immobilization ofβ-glucosidase to improve its stability and reusability.In addition to stability and reusability,pH tolerance,temperature tolerance,and enzyme kinetics are the significant parameters that illustrate the proficiency of an immobilized enzyme.The measured optimal enzymatic reaction conditions for the immobilizedβ-glucosidase were 50℃and pH 6.Furthermore,it has shown noticeable improvements in thermo-stability and pH tolerance.Temperature tolerance was observed 50%to the initial activity of the immobilized enzyme even after the 3 h of incubation at 50℃,while pH tolerance was noticed more than 50%and 40%at pH 7 and 8,respectively.The K_(m)and V_(max)values of free and immobilizedβ-glucosidase to 4-nitrophenylβ-D-glucopyranoside were 1.549μmol/L/min,0.346 mmol/L and 0.532μmol/L/min,0.080 mmol/L,respectively.The immobilizedβ-glucosidase retains its storability 80%even after 30 days of storage at 4℃and maintains 93.1%of its residual activity by reusing up to 10 cycles.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81860543,32360237)Guizhou Provincial Science and Technology Projects(Nos.ZK[2024]235,ZK[2023]Key Project 041).
文摘The escalation in the incidence of multidrug-resistant Gram-negative bacteria is becoming a pressing global concern.Polymyxin B(PMB),a conventional antibiotic with notable therapeutic efficacy against Gram-negative bacterial infections,serves as a crucial final recourse against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Nevertheless,the clinical usage of PMB is impeded by its pronounced nephrotoxicity and poor infection site targeting.This investigation is geared to construct a nanoparticle formulation(named HA-PMB@H)comprising hyaluronic acid(HA)and PMB via a simple Schiff base reaction and further coating HA by electrostatic action.HA-PMB@H shows an average size of(153.8±24.3)nm,and a mean zeta potential of(−25.6±5.2)mV.Additionally,PMB can be released from HA-PMB@H more thoroughly and efficiently at pH 5.5 compared to pH 7.4,which demonstrates the Schiff base modification of PMB paves the way for its release at focus of infection.The uptake ratio of HA-PMB@H by alveolar epithelial cells(RLE-6TN)surpassed that of free PMB devoid of HA,which facilitates to the intracellular sterilization of PMB.Furthermore,the employment of HA-PMB@H ameliorated the toxicity of PMB towards human embryonic kidney cells(HEK 293)and pulmonary microvascular endothelial cells(HULEC-5a).What is more,HA-PMB@H effectively managed severe pneumonia induced by CRKP samples from clinical patients diagnosed with CRKP infection in vivo,substantially enhancing the survival rate of mice.Consequently,this nano-delivery system holds promising clinical significance in the combat against drug-resistant bacterial infections.
基金financially supported by the National Natural Science Foundation (31525009 and 31771096)The National Key Research and Development Program of China (2017YFC1103502)+2 种基金Sichuan Innovative Research Team Program for Young Scientists (2016TD0004)Distinguished Young Scholars of Sichuan University (2011SCU04B18)1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University.
文摘Oral tyrosine kinase inhibitors(TKIs) against epidermal growth factor receptor(EGFR) family have been introduced into the clinic to treat human malignancies for decades. Despite superior properties of EGFR-TKIs as small molecule targeted drugs, their applications are still restricted due to their low solubility, capricious oral bioavailability, large requirement of daily dose, high binding tendency to plasma albumin and initial/acquired drug resistance. Nanotechnology is a promising tool to improve efficacy of these drugs. Through non-oral routes. Various nanotechnology-based delivery approaches have been developed for providing efficient delivery of EGFR-TKIs with a better pharmacokinetic profile and tissue-targeting ability. This review aims to indicate the advantage of nanocarriers for EGFR-TKIs delivery.
基金supported by the National Natural Science Foundation of China (81860543,32360237)Guizhou Provincial Science and Technology Projects (ZK[2023]+4 种基金Key Project 041,ZK[2021]076,[2019]2792 and[2018]5779-14)Guizhou Provincial Department of Education Foundation (KY[2022]229)Cultivation program of the Affiliated Hospital of Guizhou Medical University (gyfynsfc-2022-39)Cultivation program of the Guizhou Medical University (20NSP012)CR thanks the University of Hull for support
文摘Photodynamic therapy(PDT)brings new hope for the treatment of breast cancer due to few side effects and highly effective cell killing;however,the low bioavailability of traditional photosensitizers(PSs)and their dependence on oxygen severely limits their application.Aggregation-induced emission(AIE)PSs can dramatically facilitate the photosensitization effect,which can have positive impacts on tumor PDT.To-date,most AIE PSs lack tumor targeting capability and possess poor cell delivery,resulting in their use in large quantities that are harmful to healthy tissues.In this study,a series of AIE PSs based on pyridinium-substituted triphenylamine salts(TTPAs 1-6)with different alkyl chain lengths are synthesized.Results reveal that TTPAs 1-6 promote the generation of type I and II ROS,including·OH and 1O_(2).In particular,the membrane permeability and targeting of TTPAs 4-6 bearing C8-C10 side-chains are higher than TTPAs 1-3 bearing shorter alkyl chains.Additionally,they can assemble with albumin,thereby forming nanoparticles(TTPA 4-6 NPs)in situ in blood,which significantly facilitates mitochondrial-targeting and strong ROS generation ability.Moreover,the TTPA 4-6 NPs are pH-responsive,allowing for increased accumulation or endocytosis of the tumor and enhancing the imaging or therapeutic effect.Therefore,the in vivo distributions of TTPA 4-6 NPs are visually enriched in tumor sites and exhibited excellent PDT efficacy.This work demonstrates a novel strategy for AIE PDT and has the potential to play an essential role in clinical applications using nano-delivery systems.
基金financially supported by the National Natural Science Foundation of China(No.31525009,31930067,31771096)West China Precision Medicine Industrial Technology Institutes(2018-CY02-00058-GX)+4 种基金National Key Research and Development Program of China(No.2017YFC1103502)1·3·5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD18002)National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University(Z2018B06)Post-Doctor Research Project,West China Hospital,Sichuan University(2018HXBH043),China Postdoctoral Science Foundation(2019M653410)The Postdoctoral Innovation Talents Support Program(BX20180207).
文摘The prevalence of skin cancer is rising along with the rapid population aging in recent years.Traditional therapies,such as surgical treatment,radiotherapy,chemotherapy,photodynamic therapy,and immunotherapy,may accompany serious side effects,limiting their clinical benefits.According to the biological characteristics of skin cancer,we have already established two kinds of synergetic systems of photothermal therapy(microneedle)and chemotherapy,containing gold nanorods(GNR).Although the microneedle system exhibited great potential for skin cancer treatment,the system could be still improved further.So,we designed a near-infrared lightresponsive 5-fluorouracil(5-Fu)and indocyanine green(ICG)loaded monomethoxy-poly(ethylene glycol)-polycaprolactone(MPEG-PCL)nanoparticle(5-Fu-ICG-MPEG-PCL),and then 5-Fu-ICG-MPEG-PCL was integrated with a hyaluronic acid dissolvable microneedle system(HA MN)to get 5-Fu-ICG-MPEG-PCL loaded HA MN for treating skin cancers,including human epidermoid cancer and melanoma.In this system,hyaluronic acid,the microneedle carrier,possesses good skin penetration ability and is approved by FDA as a pharmaceutical adjuvant;5-Fu is recommended by FDA for skin cancer treatment;ICG,a photothermal agent,possesses a strong photothermal ability and is approved by FDA for its use in the human body.We hypothesized that 5-Fu-ICG-MPEG-PCL could be delivered by the dissolvable microneedle through the skin,and the release behavior of the drug in the nanoparticle could be controlled by near-infrared light for achieving a single-dose cure of skin cancer,improving the cure rate of skin cancer and providing a new idea and possibility for the clinical treatment of skin cancer.
基金supported by the National Natural Science Foundation of China (NSFC31930067, NSFC31771096, and NSFC31700869)the National Key Research and Development Program of China (2017YFC1103502)+1 种基金the 135 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYGD18002, China)the Post-Doctor Research Project, West China Hospital, Sichuan University (No.19HXBH099, China)。
文摘Breast cancer has become the most commonly diagnosed cancer type in the world.A combination of chemotherapy and photothermal therapy(PTT) has emerged as a promising strategy for breast cancer therapy.However,the intricacy of precise delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle.Therefore,to ensure that the therapeutic agents are synchronously delivered to the tumor site for their synergistic effect,a multifunctional nanoparticle system(PCRHNs) is developed,which is grafted onto the prussian blue nanoparticles(PB NPs) by reductionresponsive camptothecin(CPT) prodrug copolymer,and then modified with tumor-targeting peptide cyclo(Asp-D-Phe-Lys-Arg-Gly)(cRGD) and hyaluronic acid(HA).PCRHNs exhibited nano-sized structure with good monodispersity,high load efficiency of CPT,triggered CPT release in response to reduction environment,and excellent photothermal conversion under laser irradiation.Furthermore,PCRHNs can act as a photoacoustic imaging contrast agent-guided PTT.In vivo studies indicate that PCRHNs exhibited excellent bio compatibility,prolonged blood circulation,enhanced tumor accumulation,allow tumor-specific che mo-photo thermal therapy to achieve synergistic antitumor effects with reduced systemic toxicity.Moreover,hyperthermia-induced upregulation of heat shock protein 70 in the tumor cells could be inhibited by CPT.Collectively,PCRHNs may be a promising therapeutic way for breast cancer therapy.
基金funded by the National Natural Science Foundation of China(31930067,31800797,31771096,81860543,and 31525009)the National Key Research and Development Program of China(2017YFC1103502)and 1-3-5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD18002).
文摘mproving the eficacy of melanoma treatment remains an important global challenge.Here,we combined chemotherapy with protein tyrosine phosphatase nonreceptor type 2(Ptpn2)based immunotherapy in an effort to address this challenge.Shorthairpin RNA(shRNA)targeting Ptpn2 was coencapsulated with doxorubicin(DOX)in the cell membrane of MI macrophages(MIHD@RPR).The prepared nanoparticles(NPs)were effectively phagocytosed by B16F10 cells and MI macrophages,but not by MOmacrophages.Hence,NPevasion from the reticuloendothelial system(RES)was improved and NPenrichment in tumor sites increased.MIHD@RPR can directly kill tumor cells and stimulate immunogenic cell death(ICD)by DOX and downregulate Ptpn2.It can promote Ml macrophage polarization and dendritic cell maturation and increase the proportion of CD8+T cells.MIHD@RPR killed and inhibited the growth of primary melanoma and lung metastatic tumor celis without harming the surrounding tssue.These findings establish MIHD@RPR as a safe multifunctional nanoparticle capable of effectively combining chemotherapy and gene immunotherapies against melanoma.
基金financially supported by the National Natural Science Fund for Distinguished Young Scholar(NSFC31525009)National Natural Science Foundation of China(NSFC31930067,NSFC31771096,NSFC31871008,and NSFC31500809)+1 种基金the National Key Research and Development Program of China(2017YFC1103502)1·3·5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD18002).
文摘In recent years,Non-Hodgkin lymphoma(NHL)has been one of the most fast-growing malignant tumor diseases.NHL poses severe damages to physical health and a heavy burden to patients.Traditional therapies(chemotherapy or radiotherapy)bring some benefit to patients,but have severe adverse effects and do not prevent relapse.The relevance of emerging immunotherapy options(immune-checkpoint blockers or adoptive cellular methods)for NHL remains uncertain,and more intensive evaluations are needed.In this work,inspired by the idea of vaccination to promote an immune response to destroy tumors,we used a biomaterial-based strategy to improve a tumor cell-based vaccine and constructed a novel vaccine named Man-EG7/CH@CpG with antitumor properties.In this vaccine,natural tumor cells are used as a vector to load CpG-ODN,and following lethal irradiation,the formulations were decorated with mannose.The study of the characterization of the doubleimproved vaccine evidenced the enhanced ability of DCs targeting and improved immunocompetence,which displayed an antitumor function.In the lymphoma prevention model,the Man-EG7/CH@CpG vaccine restrained tumor formation with high efficiency.Furthermore,unlike the non-improved vaccine,the double-improved vaccine elicited an enhanced antitumor effect in the lymphoma treatment model.Next,to improve the moderate therapeutic effect of the mono-treatment method,we incorporated a chemotherapeutic drug(doxorubicin,DOX)into the process of vaccination and devised a combination regimen.Fortunately,a tumor inhibition rate of~85%was achieved via the combination therapy,which could not be achieved by mono-chemotherapy or mono-immunotherapy.In summary,the strategy presented here may provide a novel direction in the establishment of a tumor vaccine and is the basis for a prioritization scheme of immuno-chemotherapy in enhancing the therapeutic effect on NHL.
文摘This is an erratum to our published paper,the scale bar in Fig.6A was wrong[1].In the paper mentioned above,the scale bar in Fig.6A was wrong[1].We missed a decimal point of the scale bar.The correct scale bar of 5-Fu-ICG-MPEG-PCL@HA MN should be 1.00 mm instead of 100 mm.We have corrected the scale bar in Fig.6 as follows.
文摘This is an erratum to our published paper,the scale bar in Fig.6A was wrong[1].Erratum In the paper mentioned above, the scale bar in Fig. 6A was wrong [1]. We missed a decimal point of the scale bar. The correct scale bar of 5-Fu-ICG-MPEG-PCL@HA MN should be 1.00 mm instead of 100 mm. We have corrected the scale bar in Fig. 6 as follows.
文摘Abstract This is an erratum to our published paper,the scale bar in Fig.6A was wrong[1].Erratum In the paper mentioned above,the scale bar in Fig.6A was wrong[1].We missed a decimal point of the scale bar.The correct scale bar of 5-Fu-ICG-MPEG-PCL@HA MN should be 1.00 mm instead of 100 mm.We have corrected the scale bar in Fig.6 as follows.
文摘was wrong[1].Erratum In the paper mentioned above,the scale bar in Fig.6A was wrong[1].We missed a decimal point of the scale bar.The correct scale bar of 5-Fu-ICG-MPEG-PCL@HA MN should be 1.00 mm instead of 100 mm.We have corrected the scale bar in Fig.6 as follows.
文摘Abstract This is an erratum to our published paper,the scale bar in Fig.6A was wrong[1].Erratum In the paper mentioned above,the scale bar in Fig.6A was wrong[1].We missed a decimal point of the scale bar.The correct scale bar of 5-Fu-ICG-MPEG-PCL@HA MN should be 1.00 mm instead of 100 mm.We have corrected the scale bar in Fig.6 as follows.
文摘Nanotechnology has become the most promising domain to boost the efficiency of enzymes.Enzymes are vital as a green catalyst in many industries,food,pharmaceutical and biomedical,etc.The immobilization process of the enzyme increases its catalytic properties.In this research,a novel method is presented to describe the effect of nano-calcium carbonate on the characteristics of immobilizedβ-glucosidase,which was extracted from the Agrocybe aegirit.The nano-CaCO_(3)was produced using the eco-friendly natural deep eutectic solvent.The pure nano-CaCO_(3)was observed as vaterite,with a size of about 300 nm.The nano-calcium carbonate was coated by a natural polymer sodium alginate compound and then adsorbed chitosan.Further,this obtained composite is cross-linked by the bioactive genipin to immobilize theβ-glucosidase.The enzyme/protein loading ratio to the supports was 1:4,respectively.The recovery efficiency of immobilizedβ-glucosidase was 89.3%,and immobilization yield was 96.452%.Chitosan-coated nano-CaCO_(3)was used as a carrier for immobilization ofβ-glucosidase to improve its stability and reusability.In addition to stability and reusability,pH tolerance,temperature tolerance,and enzyme kinetics are the significant parameters that illustrate the proficiency of an immobilized enzyme.The measured optimal enzymatic reaction conditions for the immobilizedβ-glucosidase were 50℃and pH 6.Furthermore,it has shown noticeable improvements in thermo-stability and pH tolerance.Temperature tolerance was observed 50%to the initial activity of the immobilized enzyme even after the 3 h of incubation at 50℃,while pH tolerance was noticed more than 50%and 40%at pH 7 and 8,respectively.The K_(m)and V_(max)values of free and immobilizedβ-glucosidase to 4-nitrophenylβ-D-glucopyranoside were 1.549μmol/L/min,0.346 mmol/L and 0.532μmol/L/min,0.080 mmol/L,respectively.The immobilizedβ-glucosidase retains its storability 80%even after 30 days of storage at 4℃and maintains 93.1%of its residual activity by reusing up to 10 cycles.
