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Microfluidics-Enabled Nanovesicle Delivers CD47/PD-L1 Antibodies to Enhance Antitumor Immunity and Reduce Immunotoxicity in Lung Adenocarcinoma

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机构： [1]Department of Respiratory and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Department of Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, Guangdong, 518001, P. R. China. [2]Guangdong Provincial Key Laboratory of Advanced Biomaterials, Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, No. 1088 Xueyuan Rd, Nanshan District, Shenzhen, Guangdong, 518055, P. R. China. [3]School of Medicine, Life and Health Sciences, The Chinese University of Hong Kong (Shenzhen), 2001 Longxiang Road, Shenzhen, Guangdong, 518172, P. R. China. [4]Department of Hematology and Oncology, Shenzhen Children's Hospital, 7019 Yitian Road, Shenzhen, Guangdong, 518038, P. R. China. [5]Department of Pharmacology and International Cancer Center, Shenzhen University, Shenzhen, Guangdong, 518060, P. R. China. [6]Aier School of Ophthalmology, Central South University, Changsha, Hunan, 410083, P. R. China. [7]School of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong, 510632, P. R. China.

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The CD47/PD-L1 antibodies combination exhibits durable antitumor immunity but also elicits excessive immune-related adverse events (IRAEs) caused by the on-target off-tumor immunotoxicity, hindering their clinical benefits greatly. Here, a microfluidics-enabled nanovesicle using ultra-pH-sensitive polymer mannose-poly(carboxybetaine methacrylate)-poly(hydroxyethyl piperidine methacrylate) (Man-PCB-PHEP) is developed to deliver CD47/PD-L1 antibodies (NCPA) for tumor-acidity-activated immunotherapy. The NCPA can specifically release antibodies in acidic environment, thereby stimulating the phagocytosis of bone marrow-derived macrophages. In mice bearing Lewis lung carcinoma, NCPA shows significantly improved intratumoral CD47/PD-L1 antibodies accumulation, promoted tumor-associated macrophages remodeling to antitumoral status, and increased infiltration of dendritic cells and cytotoxic T lymphocytes, resulting in more favorable treatment effect compared to those of free antibodies. Additionally, NCPA also shows less IRAEs, including anemia, pneumonia, hepatitis, and small intestinal inflammation in vivo. Altogether, a potent dual checkpoint blockade immunotherapy utilizing NCPA with enhanced antitumor immunity and reduced IRAEs is demonstrated.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

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出版当年[2022]版：

大类 | 1 区

材料科学

小类 | 1 区材料科学：综合 1 区化学：综合 1 区纳米科技

最新[2025]版：

大类 | 1 区

综合性期刊

小类 | 1 区化学：综合 1 区材料科学：综合 1 区纳米科技

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出版当年[2021]版：

Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY

最新[2023]版：

Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY

影响因子： 14.3 最新[2023版] 16.3 最新五年平均 17.521 出版当年[2021版] 18.939 出版当年五年平均 16.806 出版前一年[2020版] 15.1 出版后一年[2022版]

第一作者：

第一作者机构： [1]Department of Respiratory and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Department of Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, Guangdong, 518001, P. R. China. [2]Guangdong Provincial Key Laboratory of Advanced Biomaterials, Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, No. 1088 Xueyuan Rd, Nanshan District, Shenzhen, Guangdong, 518055, P. R. China. [3]School of Medicine, Life and Health Sciences, The Chinese University of Hong Kong (Shenzhen), 2001 Longxiang Road, Shenzhen, Guangdong, 518172, P. R. China.

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通讯作者：

通讯机构： [1]Department of Respiratory and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Department of Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, Guangdong, 518001, P. R. China. [3]School of Medicine, Life and Health Sciences, The Chinese University of Hong Kong (Shenzhen), 2001 Longxiang Road, Shenzhen, Guangdong, 518172, P. R. China.

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