Rheumatoid arthritis(RA)is a sophisticated autoimmune disorder involving in the pathological characteristics of joint inflammation,synovial hyperplasia,pannus formation,cartilage destruction and bone erosion.Current r...Rheumatoid arthritis(RA)is a sophisticated autoimmune disorder involving in the pathological characteristics of joint inflammation,synovial hyperplasia,pannus formation,cartilage destruction and bone erosion.Current rheumatic therapy drugs such as non-steroidal anti-inflammatory drugs,glucocorticoids,disease-modifying antirheumatic drugs,or biologics are remarkably restricted by their poor blood circulation capability,unsatisfied drug loading efficiency,off-target irritation,and carrier-related toxicity.Recently,great efforts have concentrated on carrier-free nanoparticulated delivery strategy,and multifarious carrier-free nanodrugs including nanocrystal,nanoparticle,and nanomicelle have been manifested to possess boosted stability,extended circulation capability,enhanced drug accumulation at the inflammatory joint,and high-efficiency and low-toxicity therapeutic outcomes in RA models.Hence,this review provides a comprehensive summary of carrier-free nanodrugs for efficient RA treatment,with an emphasis on nanocrystal,nanoparticle,and nanomicelle,and then the ongoing challenges and prospects of carrier-free nanodrugs are discussed.展开更多
Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppre...Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.展开更多
Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions.Herein,we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation ...Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions.Herein,we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation followed by circularly amplified ROS-triggered drug release via positive-feedback loop.The di-selenide-bridged prodrug synthesized from vitamin E succinate and methotrexate(MTX)self-assembles into nanoparticles(VSeM);decorating acidity-cleavable PEG onto VSeM surface temporarily shields the targeting ability of MTX to evade immune clearance and consequently elongate circulation time.Upon reaching tumor sites,acidity-triggered detachment of PEG results in targeting recovery to enhance tumor cell uptake.Afterward,the VSeM could be dissociated in response to intracellular ROS to trigger VES/MTX release;then the released VES could produce extra ROS to accelerate the collapse of VSeM.Finally,the excessive ROS produced from VES could synergize with the released MTX to efficiently suppress tumor growth via orchestrated oxidation-chemotherapy.Our study provides a novel strategy to engineer cascade-responsive nanodrug for synergistic cancer treatment.展开更多
Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new...Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity.Among them,thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection.This smart biomaterial could transform to semisolid phase when the temperature increased.Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe,efficient,and sustained inner ear drug administration.This article introduces the key techniques and the latest progress in this field.展开更多
Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a ty...Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.展开更多
目的:构建基于聚乳酸—羟基乙酸共聚物(PLGA)纳米粒子的表没食子儿茶素没食子酸酯(EGCG)药物递送系统,研究其对心肌缺血损伤的作用及机制。方法:改进现有EGCG-PLGA纳米粒子(E-P-NPs)制备工艺,以透射电镜观察所制备的E-PNPs形态,并测量...目的:构建基于聚乳酸—羟基乙酸共聚物(PLGA)纳米粒子的表没食子儿茶素没食子酸酯(EGCG)药物递送系统,研究其对心肌缺血损伤的作用及机制。方法:改进现有EGCG-PLGA纳米粒子(E-P-NPs)制备工艺,以透射电镜观察所制备的E-PNPs形态,并测量聚合物分散性指数、Zeta电位、纳米粒径和载药率,进行纳米粒表征;以荧光标记法观察心肌细胞对纳米粒子的摄取情况。体外建立心肌细胞缺氧模型,体内建立小鼠急性心肌缺血损伤模型,检测不同浓度E-P-NPs对细胞活力、细胞凋亡、心肌肌钙蛋白I(cTn-I)水平及Bcl-2、Caspase9、Bax表达的影响。结果:E-P-NPs呈圆球形,多分散性指数(PDI)为0.285,平均粒径193.5 nm,电位-28.7 m V,载药率9.23%,可被心肌细胞摄取。体内、外实验研究均表明,E-P-NPs可剂量依赖性地增强心肌细胞活力,降低c Tn-I水平,降低凋亡率,上调Bcl-2蛋白表达,下调Caspase9、Bax蛋白表达,抑制细胞凋亡;E-P-NPs对缺血心肌的保护作用优于EGCG。结论:E-P-NPs粒径分布较集中,均一性较好,可通过抑制凋亡减轻心肌缺血损伤,且能使EGCG更好地发挥药效。展开更多
目的研究半乳糖化白蛋白磁性阿霉素纳米粒(Galactosed human serum Albumin Magnetic Adriamycin Nanoparticles, GAMANP)经外周静脉用药的药物毒性。探索其半数致死量,比较其与阿霉素对大鼠血液生化和外周血细胞的影响及用药后心、肝...目的研究半乳糖化白蛋白磁性阿霉素纳米粒(Galactosed human serum Albumin Magnetic Adriamycin Nanoparticles, GAMANP)经外周静脉用药的药物毒性。探索其半数致死量,比较其与阿霉素对大鼠血液生化和外周血细胞的影响及用药后心、肝、肺、肾、肠的病理表现。反复给药观察动物对该药物有无过敏反应。方法将给GAMANP的动物分为8个剂量组,每组SD大鼠10只,观察静脉给药后急性毒性试验LD50。同时设定的空白对照组和阿霉素(Adriamycin ADM)组(6组),每组10只。观察给药后各组实验大鼠的生存情况,外周血细胞的改变和血液生化及心、肝、肺、肾等脏器的病理学变化。采用Bliss法计算LD50。SPSS(11.5)统计软件统计GAMANP和阿霉素对大鼠的外周血细胞和生化指标(肝、肾功能、心肌酶学)的影响。另选同批大鼠20只分为2组,每组10只。腹腔注射GAMANP 3次后,再次皮下注射GAMANP,观察有无过敏现象发生。结果GAMANP的动物半数致死量为515.5 mg/kg(相当阿霉素22.84 mg/kg)。阿霉素半数致死量为10.38 mg/kg。前者较后者有明显的增高。同时肝、肾功能的损害和心肌酶学的改变也明显减轻。光学显微镜下的病理损害表现也明显的减轻。20只动物进行过敏实验,观察到一只动物有过敏现象。结论GAMANP是一种很好的新型改进性药物。展开更多
基金supported by the Young Elite Scientists Sponsorship Program by CACM(No.2022-QNRC2-B12)the Key Project of Anhui Province Department of Education(No.2022AH050528)+2 种基金Anhui Province Key Laboratory(No.2024ZYFBAHKLA11)the Domestic Visiting Project of Anhui Province Department of Education(No.gxgnfx2022015)the National Nature Science Foundation of China(No.82003675).
文摘Rheumatoid arthritis(RA)is a sophisticated autoimmune disorder involving in the pathological characteristics of joint inflammation,synovial hyperplasia,pannus formation,cartilage destruction and bone erosion.Current rheumatic therapy drugs such as non-steroidal anti-inflammatory drugs,glucocorticoids,disease-modifying antirheumatic drugs,or biologics are remarkably restricted by their poor blood circulation capability,unsatisfied drug loading efficiency,off-target irritation,and carrier-related toxicity.Recently,great efforts have concentrated on carrier-free nanoparticulated delivery strategy,and multifarious carrier-free nanodrugs including nanocrystal,nanoparticle,and nanomicelle have been manifested to possess boosted stability,extended circulation capability,enhanced drug accumulation at the inflammatory joint,and high-efficiency and low-toxicity therapeutic outcomes in RA models.Hence,this review provides a comprehensive summary of carrier-free nanodrugs for efficient RA treatment,with an emphasis on nanocrystal,nanoparticle,and nanomicelle,and then the ongoing challenges and prospects of carrier-free nanodrugs are discussed.
文摘Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.
基金This work was partially supported by the National Natural Science Foundation of China(Grant Nos.81871483,81671813 and 61727823)the open project funding of The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province(Grant No.2018ZDSY2001).
文摘Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions.Herein,we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation followed by circularly amplified ROS-triggered drug release via positive-feedback loop.The di-selenide-bridged prodrug synthesized from vitamin E succinate and methotrexate(MTX)self-assembles into nanoparticles(VSeM);decorating acidity-cleavable PEG onto VSeM surface temporarily shields the targeting ability of MTX to evade immune clearance and consequently elongate circulation time.Upon reaching tumor sites,acidity-triggered detachment of PEG results in targeting recovery to enhance tumor cell uptake.Afterward,the VSeM could be dissociated in response to intracellular ROS to trigger VES/MTX release;then the released VES could produce extra ROS to accelerate the collapse of VSeM.Finally,the excessive ROS produced from VES could synergize with the released MTX to efficiently suppress tumor growth via orchestrated oxidation-chemotherapy.Our study provides a novel strategy to engineer cascade-responsive nanodrug for synergistic cancer treatment.
基金supported by the national key R&D program(2022YFC2402703).
文摘Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity.Among them,thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection.This smart biomaterial could transform to semisolid phase when the temperature increased.Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe,efficient,and sustained inner ear drug administration.This article introduces the key techniques and the latest progress in this field.
文摘Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.
文摘目的:构建基于聚乳酸—羟基乙酸共聚物(PLGA)纳米粒子的表没食子儿茶素没食子酸酯(EGCG)药物递送系统,研究其对心肌缺血损伤的作用及机制。方法:改进现有EGCG-PLGA纳米粒子(E-P-NPs)制备工艺,以透射电镜观察所制备的E-PNPs形态,并测量聚合物分散性指数、Zeta电位、纳米粒径和载药率,进行纳米粒表征;以荧光标记法观察心肌细胞对纳米粒子的摄取情况。体外建立心肌细胞缺氧模型,体内建立小鼠急性心肌缺血损伤模型,检测不同浓度E-P-NPs对细胞活力、细胞凋亡、心肌肌钙蛋白I(cTn-I)水平及Bcl-2、Caspase9、Bax表达的影响。结果:E-P-NPs呈圆球形,多分散性指数(PDI)为0.285,平均粒径193.5 nm,电位-28.7 m V,载药率9.23%,可被心肌细胞摄取。体内、外实验研究均表明,E-P-NPs可剂量依赖性地增强心肌细胞活力,降低c Tn-I水平,降低凋亡率,上调Bcl-2蛋白表达,下调Caspase9、Bax蛋白表达,抑制细胞凋亡;E-P-NPs对缺血心肌的保护作用优于EGCG。结论:E-P-NPs粒径分布较集中,均一性较好,可通过抑制凋亡减轻心肌缺血损伤,且能使EGCG更好地发挥药效。
文摘目的研究半乳糖化白蛋白磁性阿霉素纳米粒(Galactosed human serum Albumin Magnetic Adriamycin Nanoparticles, GAMANP)经外周静脉用药的药物毒性。探索其半数致死量,比较其与阿霉素对大鼠血液生化和外周血细胞的影响及用药后心、肝、肺、肾、肠的病理表现。反复给药观察动物对该药物有无过敏反应。方法将给GAMANP的动物分为8个剂量组,每组SD大鼠10只,观察静脉给药后急性毒性试验LD50。同时设定的空白对照组和阿霉素(Adriamycin ADM)组(6组),每组10只。观察给药后各组实验大鼠的生存情况,外周血细胞的改变和血液生化及心、肝、肺、肾等脏器的病理学变化。采用Bliss法计算LD50。SPSS(11.5)统计软件统计GAMANP和阿霉素对大鼠的外周血细胞和生化指标(肝、肾功能、心肌酶学)的影响。另选同批大鼠20只分为2组,每组10只。腹腔注射GAMANP 3次后,再次皮下注射GAMANP,观察有无过敏现象发生。结果GAMANP的动物半数致死量为515.5 mg/kg(相当阿霉素22.84 mg/kg)。阿霉素半数致死量为10.38 mg/kg。前者较后者有明显的增高。同时肝、肾功能的损害和心肌酶学的改变也明显减轻。光学显微镜下的病理损害表现也明显的减轻。20只动物进行过敏实验,观察到一只动物有过敏现象。结论GAMANP是一种很好的新型改进性药物。
