Neutrophils as Emerging Immunotherapeutic Targets: Indirect Treatment of Tumors by Regulating the Tumor Immune Environment Based on a Sialic Acid Derivative-Modified Nanocomplex Platform

39 Pages Posted: 21 May 2021

See all articles by Meng Chen

Meng Chen

Shenyang Pharmaceutical University - School of Pharmacy

Wenjing Wu

Shenyang Pharmaceutical University - School of Pharmacy

Shuo Wang

Shenyang Pharmaceutical University - School of Pharmacy

Xiaoxue Lai

Shenyang Pharmaceutical University - School of Pharmacy

Mengyang Liu

Shenyang Pharmaceutical University - School of Pharmacy

Yiming Sun

Shenyang Pharmaceutical University - School of Pharmacy

Ying Qin

Shenyang Pharmaceutical University - School of Pharmacy

Ning Zhang

Shenyang Pharmaceutical University - School of Pharmacy

Xinrong Liu

Shenyang Pharmaceutical University - School of Pharmacy

Gang Li

Shenyang Pharmaceutical University - School of Pharmacy

Yanzhi Song

Shenyang Pharmaceutical University - School of Pharmacy

Yihui Deng

Shenyang Pharmaceutical University - School of Pharmacy

Abstract

Tumor cells are dependent on their microenvironment; thus, targeting the non-cancerous components of the tumor might lead to the development of new treatment methods. Neutrophils, which are important inflammatory cells in the tumor microenvironment (TME), significantly affect tumor cell proliferation, metastasis, angiogenesis, and immune regulation. Direct tumor targeting method results in a nanoparticle tumor distribution lower than 0.7%; therefore, targeted regulation of tumor associated neutrophil-related pathways is expected to become a new tumor therapeutic approach. Here, a sialic acid and cholesterol derivative (SA-CH) was synthesized and modified on the surface of nanocomposites to express a novel colchicine derivative (SA-EPG-BCS) for targeted immunotherapy. The interaction between the amphiphilic egg phosphatidylglycerol (EPG) structure and a newly synthesized low-toxic colchicine derivative (BCS) enables a high encapsulation rate, which greatly reduces the BCS toxicity. SA-CH modification improves the ability of the preparation to target peripheral blood neutrophils and exhibits effective anti-tumor activity in vitro and in vivo. Immunohistochemical and pathological section analyses further confirmed that SA-EPG-BCS significantly inhibited neutrophil accumulation in the tumor site, without eliciting unwanted effects. Therefore, the neutrophil migration blocking strategy using an SA-modified colchicine derivative nanocomplex, which treats the tumor indirectly by regulating the tumor immune microenvironment, may become a potential approach for cancer immunotherapy.

Suggested Citation

Chen, Meng and Wu, Wenjing and Wang, Shuo and Lai, Xiaoxue and Liu, Mengyang and Sun, Yiming and Qin, Ying and Zhang, Ning and Liu, Xinrong and Li, Gang and Song, Yanzhi and Deng, Yihui, Neutrophils as Emerging Immunotherapeutic Targets: Indirect Treatment of Tumors by Regulating the Tumor Immune Environment Based on a Sialic Acid Derivative-Modified Nanocomplex Platform. Available at SSRN: https://ssrn.com/abstract=3850524 or http://dx.doi.org/10.2139/ssrn.3850524

Meng Chen

Shenyang Pharmaceutical University - School of Pharmacy

Liaoning Province
China

Wenjing Wu

Shenyang Pharmaceutical University - School of Pharmacy

Liaoning Province
China

Shuo Wang

Shenyang Pharmaceutical University - School of Pharmacy

Liaoning Province
China

Xiaoxue Lai

Shenyang Pharmaceutical University - School of Pharmacy ( email )

Liaoning Province
China

Mengyang Liu

Shenyang Pharmaceutical University - School of Pharmacy

Liaoning Province
China

Yiming Sun

Shenyang Pharmaceutical University - School of Pharmacy

Liaoning Province
China

Ying Qin

Shenyang Pharmaceutical University - School of Pharmacy

Liaoning Province
China

Ning Zhang

Shenyang Pharmaceutical University - School of Pharmacy

Liaoning Province
China

Xinrong Liu

Shenyang Pharmaceutical University - School of Pharmacy ( email )

Liaoning Province
China

Gang Li

Shenyang Pharmaceutical University - School of Pharmacy

Liaoning Province
China

Yanzhi Song

Shenyang Pharmaceutical University - School of Pharmacy ( email )

Liaoning Province
China

Yihui Deng (Contact Author)

Shenyang Pharmaceutical University - School of Pharmacy ( email )

Liaoning Province
China

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