In Situ Reprogramming of Tumor-Associated Macrophages with Internally and Externally Engineered Exosomes

Zhang，Lingmin1,2; Lin，Yinshan2; Li，Songpei2; Guan，Xiaoling2; Jiang，Xingyu1

2023-03-06

10.1002/anie.202217089

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION   Impact Factor & Quartile

1433-7851

1521-3773

The reprogramming of tumor-associated macrophages (TAMs) has emerged as an efficient strategy for immunotherapy. However, most of the approaches did not allow the in situ reprogramming of TAM because their low efficiency, non-specificity, or potential side effects. Herein, we produced exosomes with the clustered regularly interspaced short palindromic repeats interference (CRISPRi) internally engineered and the TAM specific peptide externally engineered onto the exosome membrane. The internally and externally engineered exosomes (IEEE, also named as I3E) allowed the selective homing to tumor tissue and targeted to M2-like TAMs, which nearly repressed the expression of PI-3 kinase gamma (PI3Kγ) completely, and induced the TAMs polarizing to M1 both in vitro and in vivo. The polarized M1 macrophages awakened the “hot” tumor-immunity, causing the increase of T lymphocyte infiltration and the decrease of myeloid-derived suppressor cells, and inhibiting the tumor growth significantly. I3E reprogramed TAMs in situ precisely and efficiently.

CRISPRi Engineered Exosomes In Situ Reprogramming Lung Cancer Tumor-Associated Macrophages

SCI

English

NI Journal Papers

First ; Corresponding

National Key R&D Program of China[2018YFA0902600] ; National Natural Science Foundation of China["82072047","21535001","81730051","81673039","32071390"] ; Shenzhen Science and Technology Program[KQTD20190929172743294] ; Chinese Academy of Sciences["QYZDJ-SSW-SLH039","121D11KYSB20170026"] ; Shenzhen Bay Laboratory[SZBL2019062801004] ; Guangdong Innovative and Entrepreneurial Research Team Program[2019ZT08Y191]

Chemistry

Chemistry, Multidisciplinary

WOS:000928842200001

WILEY-V C H VERLAG GMBH

CHEMISTRY

2-s2.0-85147374580

Scopus

1.Shenzhen Key Laboratory of Smart Healthcare Engineering,Guangdong Provincial Key Laboratory of Advanced Biomaterials,Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,No. 1088 Xueyuan Rd, Nanshan District, Guangdong,518055,China
2.Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology,the NMPA and State Key Laboratory of Respiratory Disease,School of Pharmaceutical Sciences and the Fifth Affiliated Hospital,Guangzhou Medical University,Guangzhou,Guangdong,511436,China

Zhang，Lingmin,Lin，Yinshan,Li，Songpei,et al. In Situ Reprogramming of Tumor-Associated Macrophages with Internally and Externally Engineered Exosomes[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2023,62(11).

Zhang，Lingmin,Lin，Yinshan,Li，Songpei,Guan，Xiaoling,&Jiang，Xingyu.(2023).In Situ Reprogramming of Tumor-Associated Macrophages with Internally and Externally Engineered Exosomes.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,62(11).

Zhang，Lingmin,et al."In Situ Reprogramming of Tumor-Associated Macrophages with Internally and Externally Engineered Exosomes".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 62.11(2023).