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
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,an...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
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.
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.
