Reprogramming exosomes for immunity-remodeled photodynamic therapy against non-small cell lung cancer

作者全名：Guo, Jiao; Zhao, Wei; Xiao, Xinyu; Liu, Shanshan; Liu, Liang; Zhang, La; Li, Lu; Li, Zhenghang; Li, Zhi; Xu, Mengxia; Peng, Qiling; Wang, Jianwei; Wei, Yuxian; Jiang, Ning

作者地址：[Guo, Jiao; Zhao, Wei; Xiao, Xinyu; Liu, Liang; Li, Lu; Peng, Qiling; Wang, Jianwei] Chongqing Med Univ, Sch Basic Med Sci, Chongqing 400016, Peoples R China; [Liu, Shanshan] Chongqing Med Univ, Affiliated Hosp 2, Dept Plast & Maxillofacial Surg, Chongqing 400016, Peoples R China; [Zhang, La] Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Chongqing 400016, Peoples R China; [Li, Zhenghang; Wei, Yuxian] Chongqing Med Univ, Affiliated Hosp 1, Dept Breast & Thyroid Surg, Chongqing 400016, Peoples R China; [Li, Zhi; Xu, Mengxia] Tradit Chinese Med Hosp Bijie City, Bijie 551700, Guizhou, Peoples R China; [Peng, Qiling] Bijie Municipal Hlth Bur, Bijie 551700, Guizhou, Peoples R China; [Peng, Qiling] Guizhou Med Univ, Hlth Management Ctr, Affiliated Hosp, Guiyang, Peoples R China; [Jiang, Ning] Chongqing Med Univ, Sch Basic Med Sci, Dept Pathol, Chongqing 400016, Peoples R China; [Jiang, Ning] Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, Chongqing 400016, Peoples R China; [Jiang, Ning] Chongqing Med Univ, Affiliated Hosp 1, Dept Pathol, Chongqing 400016, Peoples R China

通信作者：Peng, QL; Wang, JW (通讯作者)，Chongqing Med Univ, Sch Basic Med Sci, Chongqing 400016, Peoples R China.; Wei, YX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Breast & Thyroid Surg, Chongqing 400016, Peoples R China.; Peng, QL (通讯作者)，Bijie Municipal Hlth Bur, Bijie 551700, Guizhou, Peoples R China.; Peng, QL (通讯作者)，Guizhou Med Univ, Hlth Management Ctr, Affiliated Hosp, Guiyang, Peoples R China.; Jiang, N (通讯作者)，Chongqing Med Univ, Sch Basic Med Sci, Dept Pathol, Chongqing 400016, Peoples R China.; Jiang, N (通讯作者)，Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, Chongqing 400016, Peoples R China.; Jiang, N (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Pathol, Chongqing 400016, Peoples R China.

来源：BIOACTIVE MATERIALS

ESI学科分类：　

WOS号：WOS:001249406100001

JCR分区：Q1

影响因子：18

年份：2024

卷号：39

期号：　

开始页：206

结束页：223

文献类型：Article

关键词：Non -small cell lung cancer; PDT; Immunotherapy; Tumor microenvironment; PD -L1; Targeted delivery

摘要：Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO2) nanospheres (NPs) (ICG@MnO2), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO2@Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO2 catalyzes the conversion of H2O2 to O2, thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O2 to produce singlet oxygen (1O2) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H2O2 reduces MnO2 to Mn2+, which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO2@Exo-anti-PDL1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.

基金机构：National Natural Science Foundation of China [82203310, 81972023]; Natural Science Foundation of Chongqing City [CSTC2021jcyj-msxm0172, CSTC2022nscq-msx0054]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202300478]; Creative Research Group of CQ University [CXQT21017]; Program for Youth Innovation in Future Medicine from Chongqing Medical University

基金资助正文：This work was supported by National Natural Science Foundation of China (Grant No. 82203310 and No. 81972023) ; Natural Science Foundation of Chongqing City (Grant No. CSTC2021jcyj-msxm0172 and CSTC2022nscq-msx0054) ; Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No. KJQN202300478) ; Creative Research Group of CQ University (Grant No. CXQT21017) and Program for Youth Innovation in Future Medicine from Chongqing Medical University.