Cell membrane-derived nanoparticles(NPs)have recently gained popularity due to their desirable features in drug delivery such as mimicking properties of native cells,impeding systemic clearance,and altering foreign bo...Cell membrane-derived nanoparticles(NPs)have recently gained popularity due to their desirable features in drug delivery such as mimicking properties of native cells,impeding systemic clearance,and altering foreign body responses.Besides NP technology,adoptive immunotherapy has emerged due to its promise in cancer specificity and therapeutic efficacy.In this research,we developed a biomimetic drug carrier based on chimeric antigen receptor(CAR)transduced T-cell membranes.For that purpose,anti-HER2 CAR-T cells were engineered via lentiviral transduction of anti-HER2 CAR coding lentiviral plasmids.Anti-HER2 CAR-T cells were characterized by their specific activities against the HER2 antigen and used for cell membrane extraction.Anti-cancer drug Cisplatin-loaded poly(D,L-lactide-co-glycolic acid)(PLGA)NPs were coated with anti-human epidermal growth factor receptor 2(HER2)-specific CAR engineered T-cell membranes.Anti-HER2 CAR-T-cell membrane-coated PLGA NPs(CAR-T-MNPs)were characterized and confirmed via fluorescent microscopy and flow cytometry.Membrane-coated NPs showed a sustained drug release over the course of 21 days in physiological conditions.Cisplatin-loaded CAR-T-MNPs also inhibited the growth of multiple HER2+cancer cells in vitro.In addition,in vitro uptake studies revealed that CAR-T-MNPs showed an increased uptake by A549 cells.These results were also confirmed via in vivo biodistribution and therapeutic studies using a subcutaneous lung cancer model in nude mice.CAR-T-MNPs localized preferentially at tumor areas compared to those of other studied groups and consisted of a significant reduction in tumor growth in tumor-bearing mice.In Conclusion,the new CAR modified cell membrane-coated NP drug-delivery platform has demonstrated its efficacy both in vitro and in vivo.Therefore,CAR engineered membrane-coated NP system could be a promising cell-mimicking drug carrier that could improve therapeutic outcomes of lung cancer treatments.展开更多
Nanotechnology-based drug delivery platforms have been developed over the last two decades because of their favorable features in terms of improved drug bioavailability and stability.Despite recent advancement in nano...Nanotechnology-based drug delivery platforms have been developed over the last two decades because of their favorable features in terms of improved drug bioavailability and stability.Despite recent advancement in nanotechnology platforms,this approach still falls short to meet the complexity of biological systems and diseases,such as avoiding systemic side effects,manipulating biological interactions and overcoming drug resistance,which hinders the therapeutic outcomes of the NP-based drug delivery systems.To address these issues,various strategies have been developed including the use of engineered cells and/or cell membrane-coated nanocarriers.Cell membrane receptor profiles and characteristics are vital in performing therapeutic functions,targeting,and homing of either engineered cells or cell membrane-coated nanocarriers to the sites of interest.In this context,we comprehensively discuss various cell-and cell membrane-based drug delivery approaches towards cancer therapy,the therapeutic potential of these strategies,and the limitations associated with engineered cells as drug carriers and cell membrane-associated drug nanocarriers.Finally,we review various cell types and cell membrane receptors for their potential in targeting,immunomodulation and overcoming drug resistance in cancer.展开更多
基金supported by the Cancer Prevention&Research Institute of Texas(CPRIT)High-Impact/High-Risk Research Awards#RP210206.
文摘Cell membrane-derived nanoparticles(NPs)have recently gained popularity due to their desirable features in drug delivery such as mimicking properties of native cells,impeding systemic clearance,and altering foreign body responses.Besides NP technology,adoptive immunotherapy has emerged due to its promise in cancer specificity and therapeutic efficacy.In this research,we developed a biomimetic drug carrier based on chimeric antigen receptor(CAR)transduced T-cell membranes.For that purpose,anti-HER2 CAR-T cells were engineered via lentiviral transduction of anti-HER2 CAR coding lentiviral plasmids.Anti-HER2 CAR-T cells were characterized by their specific activities against the HER2 antigen and used for cell membrane extraction.Anti-cancer drug Cisplatin-loaded poly(D,L-lactide-co-glycolic acid)(PLGA)NPs were coated with anti-human epidermal growth factor receptor 2(HER2)-specific CAR engineered T-cell membranes.Anti-HER2 CAR-T-cell membrane-coated PLGA NPs(CAR-T-MNPs)were characterized and confirmed via fluorescent microscopy and flow cytometry.Membrane-coated NPs showed a sustained drug release over the course of 21 days in physiological conditions.Cisplatin-loaded CAR-T-MNPs also inhibited the growth of multiple HER2+cancer cells in vitro.In addition,in vitro uptake studies revealed that CAR-T-MNPs showed an increased uptake by A549 cells.These results were also confirmed via in vivo biodistribution and therapeutic studies using a subcutaneous lung cancer model in nude mice.CAR-T-MNPs localized preferentially at tumor areas compared to those of other studied groups and consisted of a significant reduction in tumor growth in tumor-bearing mice.In Conclusion,the new CAR modified cell membrane-coated NP drug-delivery platform has demonstrated its efficacy both in vitro and in vivo.Therefore,CAR engineered membrane-coated NP system could be a promising cell-mimicking drug carrier that could improve therapeutic outcomes of lung cancer treatments.
基金This work was partially supported by the National Institute of Health Award(T32 HL134613,KTN)Yaman S was supported by the Turkish Ministry of National Education.
文摘Nanotechnology-based drug delivery platforms have been developed over the last two decades because of their favorable features in terms of improved drug bioavailability and stability.Despite recent advancement in nanotechnology platforms,this approach still falls short to meet the complexity of biological systems and diseases,such as avoiding systemic side effects,manipulating biological interactions and overcoming drug resistance,which hinders the therapeutic outcomes of the NP-based drug delivery systems.To address these issues,various strategies have been developed including the use of engineered cells and/or cell membrane-coated nanocarriers.Cell membrane receptor profiles and characteristics are vital in performing therapeutic functions,targeting,and homing of either engineered cells or cell membrane-coated nanocarriers to the sites of interest.In this context,we comprehensively discuss various cell-and cell membrane-based drug delivery approaches towards cancer therapy,the therapeutic potential of these strategies,and the limitations associated with engineered cells as drug carriers and cell membrane-associated drug nanocarriers.Finally,we review various cell types and cell membrane receptors for their potential in targeting,immunomodulation and overcoming drug resistance in cancer.
