Anti-TNFR2 Antibody-Conjugated PLGA Nanoparticles for Targeted Delivery of Adriamycin in Mouse Colon Cancer

被引：2

作者：

Li, Ping ^{[1
,2
]}

Yang, Yang ^{[1
]}

Wang, Yifei ^{[1
]}

Zheng, Jingbin ^{[1
]}

Chen, Fengyang ^{[1
]}

Jiang, Mengmeng ^{[1
]}

Chou, Chon-kit ^{[1
]}

Cong, Weihong ^{[3
]}

Li, Zongjin ^{[4
]}

Chen, Xin ^{[1
,5
,6
]}

机构：

[1] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China

[2] Chinese Acad Sci, Inst Biomed & Biotechnol, Shenzhen Inst Adv Technol, Ctr Canc Immunol, Shenzhen, Peoples R China

[3] China Acad Chinese Med Sci, Lab Cardiovasc Dis, Xiyuan Hosp, Beijing, Peoples R China

[4] Macau Univ Sci & Technol, Fac Innovat Engn, Macau, Peoples R China

[5] Univ Macau, Fac Hlth Sci, Dept Pharmaceut Sci, Macau, Peoples R China

[6] Univ Macau, MoE Frontiers Sci Ctr Precis Oncol, Macau, Peoples R China

来源：

RESEARCH | 2024年 / 7卷

基金：

中国国家自然科学基金;

关键词：

REGULATORY T-CELLS; TUMOR; TNFR2; DRUG; IMMUNOLOGY; IMMUNITY; GROWTH;

D O I：

10.34133/research.0444

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

High levels of tumor necrosis factor receptor type II (TNFR2) are preferentially expressed by immunosuppressive CD4+Foxp3+ regulatory T cells (Tregs), especially those present in the tumor microenvironment, as initially reported by us. There is compelling evidence that targeting TNFR2 markedly enhances antitumor immune responses. Furthermore, a broad spectrum of human cancers also expresses TNFR2, while its expression by normal tissue is very limited. We thus hypothesized that TNFR2 may be harnessed for tumor-targeted delivery of chemotherapeutic agents. In this study, we performed a proof-of-concept study by constructing a TNFR2-targeted PEGylated poly(dl-lactic-co-glycolic acid) (PLGA-PEG) nanodrug delivery system [designated as TNFR2-PLGA-ADR (Adriamycin)]. The results of in vitro study showed that this TNFR2-targeted delivery system had the properties in cellular binding and cytotoxicity toward mouse colon cancer cells. Further, upon intravenous injection, TNFR2-PLGA-ADR could efficiently accumulate in MC38 and CT26 mouse colon tumor tissues and preferentially bind with tumor-infiltrating Tregs. Compared with ADR and ISO-PLGA-ADR, the in vivo antitumor effect of TNFR2-PLGA-ADR was markedly enhanced, which was associated with a decrease of TNFR2+ Tregs and an increase of IFN gamma+CD8+ cytotoxic T lymphocytes in the tumor tissue. Therefore, our results clearly show that targeting TNFR2 is a promising strategy for designing tumor-specific chemoimmunotherapeutic agent delivery system.

引用

页数：17