Macrophage Membrane-Coated Nano- Gemcitabine Promotes Lymphocyte Infiltration and Synergizes AntiPD-L1 to Restore the Tumoricidal Function

被引:50
作者
Li, Jie [1 ,2 ,3 ]
Wu, Yao [1 ,2 ,4 ,5 ]
Wang, Jiaoying [1 ,2 ]
Xu, Xiaoxuan [1 ,2 ]
Zhang, Ao [6 ]
Li, Yaping [1 ,2 ,7 ]
Zhang, Zhiwen [4 ,5 ]
机构
[1] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
[2] Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
[3] Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai, Shandong, Peoples R China
[4] Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
[5] Fudan Univ, Key Lab Smart Drug Delivery, Minist Educ, Shanghai 201203, Peoples R China
[6] Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China
[7] Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
基金
中国博士后科学基金; 国家重点研发计划; 中国国家自然科学基金;
关键词
gemcitabine; macrophage; nanoparticle; lymphocytes infiltration; immunotherapy; LUNG METASTASIS; T-CELL; CANCER; TUMORS; CHEMOTHERAPY; PH;
D O I
10.1021/acsnano.2c07861
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The limited lymphocyte infiltration and exhaus-tion of tumoricidal functions in solid tumors remain a formidable obstacle to cancer immunotherapy. Herein, we designed a macrophage membrane-coated nano-gemcitabine system (MNGs) to promote lymphocyte infiltration and then synergized anti-programmed death ligand 1 (antiPD-L1) to reinvigorate the exhausted lymphocytes. MNGs exhibited effective intratumor-permeating and responsive drug-releasing capacity, produced notable elimination of versatile immuno-suppressive cells, and promoted lymphocyte infiltration into cancer cell regions in tumors, but over 50% of these infiltrated lymphocytes were in the exhausted state. Compared with MNG monotherapy, the MNGs+antiPD-L1 combination produced 31.77% and 30.63% reduction of exhausted CD3+CD8+ T cells and natural triller (NK) cells and 2.83-and 3.17-fold increases of interferon-gamma (IFN-gamma)-positive subtypes, respectively, thereby resulting in considerable therapeutic benefits in several tumor models. Thus, MNGs provide an encouraging strategy to promote lymphocyte infiltration and synergize antiPD-L1 to restore their tumoricidal function for cancer immunotherapy.
引用
收藏
页码:322 / 336
页数:15
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