A variety of nano-engineered photosensitizers have been developed for photodynamic therapy(PDT)of cancer diseases. However, traditional nano-engineering methods usually cannot avoid drug leakage and premature release,...A variety of nano-engineered photosensitizers have been developed for photodynamic therapy(PDT)of cancer diseases. However, traditional nano-engineering methods usually cannot avoid drug leakage and premature release, and have disadvantages such as low drug load and inaccurate release.The self-assembly strategy based on amphiphilic peptides has been considered to be more attractive nano-engineering method. Here we developed novel acid-activatable self-assembled nanophotosensitizers based on an amphiphilic peptide derivative. The peptide derivative was synthesized from a fluorescein molecule with thermally activated delayed fluorescence(TADF). The self-assembled nanophotosensitizers can specifically enter the tumor cells and disassemble inside lysosomes companied with “turn-on” fluorescence and photodynamic therapy effect. Such smart nanophotosensitizers will open new opportunities for cancer theranostics.展开更多
Cyclin-dependent kinases 4 and 6 inhibitors(CDK4/6i)have been demonstrated to trigger antitumor immunity for tumor regression.However,the therapeutic performance of CDK4/6i-meadiated cancer immunotherapy was impaired ...Cyclin-dependent kinases 4 and 6 inhibitors(CDK4/6i)have been demonstrated to trigger antitumor immunity for tumor regression.However,the therapeutic performance of CDK4/6i-meadiated cancer immunotherapy was impaired by the immunosuppressive tumor microenvironment(ITM)due to overexpression of programmed death ligand 1(PD-L1)on the surface of cancer cell membrane.To improve the immunotherapeutic performance of CDK4/6i,we herein developed endosomal acidactivatable micelleplex for si RNA delivery and PD-L1 knockdown in the tumor cells in vitro and in vivo.We further demonstrated that the combination of PD-L1 knockdown and CDK4/6 inhibition facilitated intratumoral infiltration of cytotoxic T lymphocytes(CTLs),and elicited protective immune response and efficiently suppressed tumor growth in vivo.This study revealed the importance of molecular design of the micelleplex for highly efficient si RNA delivery,which might provide a novel insight for RNAi-based cancer immunotherapy.展开更多
基金financially supported by the National Natural Science Foundation of China (No. 21877011)the Fundamental Research Funds for the Central Universities (No. DUT20YG119)the Talent Fund of Shandong Collaborative Innovation Center of Eco-Chemical Engineering (No. XTCXYX03)。
文摘A variety of nano-engineered photosensitizers have been developed for photodynamic therapy(PDT)of cancer diseases. However, traditional nano-engineering methods usually cannot avoid drug leakage and premature release, and have disadvantages such as low drug load and inaccurate release.The self-assembly strategy based on amphiphilic peptides has been considered to be more attractive nano-engineering method. Here we developed novel acid-activatable self-assembled nanophotosensitizers based on an amphiphilic peptide derivative. The peptide derivative was synthesized from a fluorescein molecule with thermally activated delayed fluorescence(TADF). The self-assembled nanophotosensitizers can specifically enter the tumor cells and disassemble inside lysosomes companied with “turn-on” fluorescence and photodynamic therapy effect. Such smart nanophotosensitizers will open new opportunities for cancer theranostics.
基金financially supported by the National Natural Science Foundation of China(Nos.51873228 and 31671024)Basic Research Program of Shenzhen(No.JCYJ20180227175420974)+1 种基金Science and Technology Development Fund,Macao SAR(No.083/2017/A2)Open Research Fund of State Key Laboratory of Polymer Physics and Chemistry,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences。
文摘Cyclin-dependent kinases 4 and 6 inhibitors(CDK4/6i)have been demonstrated to trigger antitumor immunity for tumor regression.However,the therapeutic performance of CDK4/6i-meadiated cancer immunotherapy was impaired by the immunosuppressive tumor microenvironment(ITM)due to overexpression of programmed death ligand 1(PD-L1)on the surface of cancer cell membrane.To improve the immunotherapeutic performance of CDK4/6i,we herein developed endosomal acidactivatable micelleplex for si RNA delivery and PD-L1 knockdown in the tumor cells in vitro and in vivo.We further demonstrated that the combination of PD-L1 knockdown and CDK4/6 inhibition facilitated intratumoral infiltration of cytotoxic T lymphocytes(CTLs),and elicited protective immune response and efficiently suppressed tumor growth in vivo.This study revealed the importance of molecular design of the micelleplex for highly efficient si RNA delivery,which might provide a novel insight for RNAi-based cancer immunotherapy.
