Allomelanin-based biomimetic nanotherapeutics for orthotopic glioblastoma targeted photothermal immunotherapy

作者全名："Sun, Maoyuan; Li, Yan; Zhang, Wenli; Gu, Xiang; Wen, Rong; Zhang, Ke; Mao, Jinning; Huang, Chengyao; Zhang, Xiong; Nie, Mao; Zhang, Zhiwen; Qi, Chao; Cai, Kaiyong; Liu, Guodong"

作者地址："[Sun, Maoyuan; Wen, Rong; Liu, Guodong] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing 400016, Peoples R China; [Li, Yan; Gu, Xiang; Zhang, Ke; Huang, Chengyao; Qi, Chao; Cai, Kaiyong] Chongqing Univ, Coll Bioengn, Key Lab Biorheol Sci & Technol, Minist Educ, Chongqing 400044, Peoples R China; [Zhang, Wenli] Chongqing Med Univ, Affiliated Hosp 2, Dept Radiol, Chongqing 400016, Peoples R China; [Mao, Jinning] Chongqing Med Univ, Affiliated Hosp 2, Hlth management Ctr, Chongqing 400016, Peoples R China; [Zhang, Xiong] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing 400016, Peoples R China; [Nie, Mao] Chongqing Med Univ, Affiliated Hosp 2, Dept Orthoped, Chongqing 400016, Peoples R China; [Zhang, Zhiwen] Fudan Univ, Sch Pharm & Key Lab Smart Drug Delivery, Minist Educ, Shanghai 201203, Peoples R China"

通信作者："Liu, GD (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing 400016, Peoples R China.; Qi, C; Cai, KY (通讯作者)，Chongqing Univ, Coll Bioengn, Key Lab Biorheol Sci & Technol, Minist Educ, Chongqing 400044, Peoples R China."

来源：ACTA BIOMATERIALIA

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001031515100001

JCR分区：Q1

影响因子：9.4

年份：2023

卷号：166

期号：　

开始页：552

结束页：566

文献类型：Article

关键词：Glioblastoma; Allomelanin; Tumor immunotherapy; Immune checkpoint blockade; Photothermal therapy

摘要："Immune checkpoint blockade (ICB) therapy has shown great potential in the treatment of malignant tumors, but its therapeutic effect on glioblastoma (GBM) is unsatisfactory because of the low immunogenicity and T cell infiltration, as well as the presence of blood-brain barrier (BBB) that blocks most of ICB agents to the GBM tissues. Herein, we developed a biomimetic nanoplatform of AMNP@CLP@CCM for GBM-targeted photothermal therapy (PTT) and ICB synergistic therapy by loading immune checkpoint inhibitor CLP002 into the allomelanin nanoparticles (AMNPs) and followed by coating cancer cell membranes (CCM). The resulting AMNP@CLP@CCM can successfully cross the BBB and deliver CLP002 to GBM tissues due to the homing effect of CCM. As a natural photothermal conversion agent, AMNPs are used for tumor PTT. The increased local temperature by PTT not only enhances BBB penetration but also upregulates the PD-L1 level on GBM cells. Importantly, PTT can effectively stimulate immunogenic cell death to induce tumor-associated antigen exposure and promote T lymphocyte infiltration, which can further amplify the antitumor immune responses of GBM cells to CLP002-mediated ICB therapy, resulting in significant growth inhibition of the orthotopic GBM. Therefore, AMNP@CLP@CCM has great potential for the treatment of orthotopic GBM by PTT and ICB synergistic therapy."

基金机构："National Natural Science Foundation of China [51802202, 21807074, 81401500]; Natural Science Foundation of Chongqing [cstc2021jcyj-cxttX0002, cstc2019jcyj-msxmX0231]; Chongqing Talents: Youth Top-notch Talent Project [cstc2022ycjh-bgzxm0167]; Kuan-ren Talents Program of the Second Affiliated Hospital of Chongqing Medical University, Chongqing Scientific and Health Joint Medical Research Project [2020GDRC021]; Chongqing Postgraduate Research Innovation Project [CYS 22347]"

基金资助正文："This work was financially supported by the National Natural Science Foundation of China (51802202 , 21807074 , and 81401500) , the Natural Science Foundation of Chongqing (cstc2021jcyj-cxttX0002 and cstc2019jcyj-msxmX0231) , Chongqing Talents: Youth Top-notch Talent Project (cstc2022ycjh-bgzxm0167) , Kuan-ren Talents Program of the Second Affiliated Hospital of Chongqing Medical University, Chongqing Scientific and Health Joint Medical Research Project (2020GDRC021) , and Chongqing Postgraduate Research Innovation Project (CYS 22347) ."