An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal  

作　　者：Yanan Sun Bochen Lyu Chang Yang Bing He Hua Zhang Xueqing Wang Qiang Zhang Wenbing Dai 

机构地区：[1]Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems,State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing,100191,China [2]Department of Pharmaceutics,School of Pharmaceutical Sciences,Hebei Medical University,Shijiazhuang,050017,China

出　　处：《Bioactive Materials》2023年第4期47-59,共13页生物活性材料（英文）

基　　金：This work was supported by the National Key R&D Program of China(2017YFA0205600);Natural Science Foundation of Hebei Province(H2022206171)。

摘　　要：Mild photothermal therapy combined with immune checkpoint blockade has received increasing attention for the treatment of advanced or metastatic cancers due to its good therapeutic efficacy.However,it remains a challenge to facilely integrate the two therapies and make it potential for clinical translation.This work designed a peptide-photosensitizer conjugate(PPC),which consisted of a PD-L1 antagonist peptide(CVRARTR),an MMP-2 specific cleavable sequence,a self-assembling motif,and the photosensitizer Purpurin 18.The single-component PPC can self-assemble into nanospheres which is suitable for intravenous injection.The PPC nanosphere is cleaved by MMP-2 when it accumulates in tumor sites,thereby initiating the cancer-specific release of the antagonist peptide.Simultaneously,the nanospheres gradually transform into co-assembled nanofibers,which promotes the retention of the remaining parts within the tumor.In vivo studies demonstrated that PPC nanospheres under laser irradiation promote the infiltration of cytotoxic T lymphocytes and maturation of DCs,which sensitize 4T1 tumor cells to immune checkpoint blockade therapy.Therefore,PPC nanospheres inhibit tumor growth efficiently both in situ and distally and blocked the formation of lung metastases.The present study provides a simple and efficient integrated strategy for breast cancer photoimmunotherapy.

关 键 词：Transformable nanomedicine Self-assembled peptide Immune checkpoint blockade Photothermal therapy Photoimmunotherapy 

分 类 号：TB33[一般工业技术—材料科学与工程]