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In Situ Reprogramming of Tumor-Associated Macrophages with Internally and Externally Engineered Exosomes |
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| Authors: | Dr Lingmin Zhang Yinshan Lin Dr Songpei Li Xiaoling Guan Xingyu Jiang |
| Institution: | 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, No. 1088 Xueyuan Rd, Nanshan District, 518055 Shenzhen, Guangdong, China
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, 511436 Guangzhou, Guangdong, China These authors contributed equally to this work. Contribution: Conceptualization (lead), Formal analysis (equal), Funding acquisition (equal), Project administration (equal), Supervision (equal), Writing - review & editing (lead);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, 511436 Guangzhou, Guangdong, China These authors contributed equally to this work. Contribution: Data curation (lead), Formal analysis (lead), Methodology (lead), Software (lead), Validation (lead), Visualization (lead);3. 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, 511436 Guangzhou, Guangdong, China These authors contributed equally to this work. Contribution: ?Investigation (equal), Methodology (equal), Software (equal), Writing - original draft (lead);4. 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, 511436 Guangzhou, Guangdong, China Contribution: ?Investigation (supporting), Methodology (supporting), Software (supporting), Validation (supporting);5. Shenzhen Key Laboratory of Smart Healthcare Engineering, Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, No. 1088 Xueyuan Rd, Nanshan District, 518055 Shenzhen, Guangdong, China |
| Abstract: | 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 i nternally and e xternally e ngineered e xosomes ( 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. |
| Keywords: | CRISPRi Engineered Exosomes In Situ Reprogramming Lung Cancer Tumor-Associated Macrophages |