Due to the limitations of conventional chemotherapy including side effects,poor prognosis,and drug resistance,there is an urgent need for the development of a novel multi-functional combined therapy strategy.Dopamine-...Due to the limitations of conventional chemotherapy including side effects,poor prognosis,and drug resistance,there is an urgent need for the development of a novel multi-functional combined therapy strategy.Dopamine-modified oxaliplatin prodrug(OXA-DA)was successfully synthesized in this study to ameliorate the organ distribution of oxaliplatin for improving the drug efficacy and reducing toxic side effects,and OXA-DA was applied to develop a porous oxaliplatin cross-linked polydopamine nanoparticle for loading siPD-L1 to construct multifunctional nanoplatform.The multifunctional nanoplatform was modified with poly(2-ethyl-2-oxazoline)(PEOz),which occurred charge reversal in the tumor microenvironment,and exerted the lysosomal escape effect in tumor cells to improve the bioavailability of small interfering RNA targeting programmed cell death-ligand 1(siPD-L1).The pH-responsive charge reversal,photothermal,biodegradation,lysosomal escape ability,PD-L1 protein degradation,toxicity properties and multiple antitumor effects were comprehensively evaluated in vitro and in vivo experiments.The findings indicated that OXA-DA-siPD-L1@PDA-PEOz excellently induced tumor cell necrosis and apoptosis as a result of the synergistic effect of chemo-photothermal therapy,and upregulated CD8+T cells produced interferon-γ(IFN-γ)to further attack the tumor cells.In conclusion,the novel nanoplatform-mediated chemo/photothermal/immunotherapy has promising clinical applications in the treatment of malignant tumors.展开更多
Photodynamic therapy (PDT) is new modality for a number of diseases such as cancer, based on the combination of a lesion-localizing photosensitizer (PS) with light exposure to
基金the National Natural Science Foundation of China(Nos.32071342 and 32101065)the Natural Science Foundation of Guangdong Province(Nos.2023A1515012015,2022A1515110271 and 2020A1515011353).
文摘Due to the limitations of conventional chemotherapy including side effects,poor prognosis,and drug resistance,there is an urgent need for the development of a novel multi-functional combined therapy strategy.Dopamine-modified oxaliplatin prodrug(OXA-DA)was successfully synthesized in this study to ameliorate the organ distribution of oxaliplatin for improving the drug efficacy and reducing toxic side effects,and OXA-DA was applied to develop a porous oxaliplatin cross-linked polydopamine nanoparticle for loading siPD-L1 to construct multifunctional nanoplatform.The multifunctional nanoplatform was modified with poly(2-ethyl-2-oxazoline)(PEOz),which occurred charge reversal in the tumor microenvironment,and exerted the lysosomal escape effect in tumor cells to improve the bioavailability of small interfering RNA targeting programmed cell death-ligand 1(siPD-L1).The pH-responsive charge reversal,photothermal,biodegradation,lysosomal escape ability,PD-L1 protein degradation,toxicity properties and multiple antitumor effects were comprehensively evaluated in vitro and in vivo experiments.The findings indicated that OXA-DA-siPD-L1@PDA-PEOz excellently induced tumor cell necrosis and apoptosis as a result of the synergistic effect of chemo-photothermal therapy,and upregulated CD8+T cells produced interferon-γ(IFN-γ)to further attack the tumor cells.In conclusion,the novel nanoplatform-mediated chemo/photothermal/immunotherapy has promising clinical applications in the treatment of malignant tumors.
文摘Photodynamic therapy (PDT) is new modality for a number of diseases such as cancer, based on the combination of a lesion-localizing photosensitizer (PS) with light exposure to
