Cellular nanovesicles which are referred to as cell-derived,nanosized lipid bilayer structures,have emerged as a promising platform for regulating immune responses.Owing to their outstanding advantages such as high bi...Cellular nanovesicles which are referred to as cell-derived,nanosized lipid bilayer structures,have emerged as a promising platform for regulating immune responses.Owing to their outstanding advantages such as high biocompatibility,prominent structural stability,and high loading capacity,cellular nanovesicles are suitable for delivering various immunomodulatory molecules,such as small molecules,nucleic acids,peptides,and proteins.Immunomodulation induced by cellular nanovesicles has been exploited to modulate immune cell behaviors,which is considered as a novel cell-free immunotherapeutic strategy for the prevention and treatment of diverse diseases.Here we review emerging concepts and new advances in leveraging cellular nanovesicles to activate or suppress immune responses,with the aim to explicate their applications for immunomodulation.We overview the general considerations and principles for the design of engineered cellular nanovesicles with tailored immunomodulatory activities.We also discuss new advances in engineering cellular nanovesicles as immunotherapies for treating major diseases.展开更多
Pulmonary hypertension(PH)is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated.The hyperproliferation and apoptosis resistance of pulmonar...Pulmonary hypertension(PH)is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated.The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells(PASMCs)contributes to pulmonary vascular remodeling in pulmonary hypertension,which is closely linked to the downregulation of forkhead box transcriptional factor O1(FoxO1)and apoptotic protein caspase 3(Cas-3).Here,PA-targeted co-delivery of a FoxO1 stimulus(paclitaxel,PTX)and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension.The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles,followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs.The co-loaded system(170 nm)circulates in the blood over time,accumulates in the lung,effectively targets the PAs,and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics,leading to a decrease in pulmonary arterial pressure and Fulton's index.Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis.Taken together,this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.展开更多
Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for t...Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for the treatment of IFIs,amphotericin B(AmB)is the most frequently used drug.AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance.In this review,we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs.We have also discussed the mechanism of actions of AmB,rationale for treating IFIs,and recent advances in formulating AmB for clinical use.Finally,this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.展开更多
基金support from the College of Pharmacy at University of Illinois Chicago。
文摘Cellular nanovesicles which are referred to as cell-derived,nanosized lipid bilayer structures,have emerged as a promising platform for regulating immune responses.Owing to their outstanding advantages such as high biocompatibility,prominent structural stability,and high loading capacity,cellular nanovesicles are suitable for delivering various immunomodulatory molecules,such as small molecules,nucleic acids,peptides,and proteins.Immunomodulation induced by cellular nanovesicles has been exploited to modulate immune cell behaviors,which is considered as a novel cell-free immunotherapeutic strategy for the prevention and treatment of diverse diseases.Here we review emerging concepts and new advances in leveraging cellular nanovesicles to activate or suppress immune responses,with the aim to explicate their applications for immunomodulation.We overview the general considerations and principles for the design of engineered cellular nanovesicles with tailored immunomodulatory activities.We also discuss new advances in engineering cellular nanovesicles as immunotherapies for treating major diseases.
基金supported by the National Natural Science Foundation of China(81872823,82073782,and 82170063)the Shanghai Science and Technology Committee(19430741500,China)+3 种基金the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(zdsys-202103,China)the Medical Science and Technique Development Foundation of Nanjing Municipal Government(QRX17013,China)the Key Project from Medical Science and Technique Development Foundation of Nanjing Municipal Government(ZKX20017,China)the Science Foundation of Ministry of Health of Jiangsu Province in China(ZDA2020016)。
文摘Pulmonary hypertension(PH)is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated.The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells(PASMCs)contributes to pulmonary vascular remodeling in pulmonary hypertension,which is closely linked to the downregulation of forkhead box transcriptional factor O1(FoxO1)and apoptotic protein caspase 3(Cas-3).Here,PA-targeted co-delivery of a FoxO1 stimulus(paclitaxel,PTX)and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension.The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles,followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs.The co-loaded system(170 nm)circulates in the blood over time,accumulates in the lung,effectively targets the PAs,and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics,leading to a decrease in pulmonary arterial pressure and Fulton's index.Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis.Taken together,this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.
基金supported by the National Natural Science Foundation of China(Nos.81872823,81871477 and 82073782)the Double First-Class(CPU2018PZQ13,China)of the China Pharmaceutical University+3 种基金the Shanghai Science and Technology Committee(No.19430741500)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(TCM-201905,China)the Guangdong Basic and Applied Basic Research Foundation,China(No.2020A1515010593)the Fundamental Research Funds for Central Universities(No.20ykpy111,China)
文摘Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for the treatment of IFIs,amphotericin B(AmB)is the most frequently used drug.AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance.In this review,we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs.We have also discussed the mechanism of actions of AmB,rationale for treating IFIs,and recent advances in formulating AmB for clinical use.Finally,this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.
