A novel fluorinated polyethyleneimine with microRNA-942-5p-sponges polyplex gene delivery system for non-small-cell lung cancer therapy

Yi Jin; Wei Yu; Wenkai Zhang; Chen Wang; Yao Liu; Wei-En Yuan; Yun Feng

doi:10.1016/j.jcis.2023.05.153

A novel fluorinated polyethyleneimine with microRNA-942-5p-sponges polyplex gene delivery system for non-small-cell lung cancer therapy

J Colloid Interface Sci. 2023 Oct 15:648:287-298. doi: 10.1016/j.jcis.2023.05.153. Epub 2023 May 29.

Authors

Yi Jin¹, Wei Yu¹, Wenkai Zhang¹, Chen Wang², Yao Liu¹, Wei-En Yuan³, Yun Feng⁴

Affiliations

¹ Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China., National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China.
² Department of Respiration, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Kunming University of Science and Technology, Kunming, China.
³ Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China., National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: yuanweien@sjtu.edu.cn.
⁴ Department of Respiration, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Kunming University of Science and Technology, Kunming, China. Electronic address: fy01057@163.com.

PMID: 37301153
DOI: 10.1016/j.jcis.2023.05.153

Abstract

Gene delivery for non-small-cell lung cancer treatment has been a challenge due to low nucleic acid binding ability, cell-wall barrier, and high cytotoxicity. Cationic polymers, such as the traditional "golden standard" polyethyleneimine (PEI) 25 kDa have emerged as a promising carrier for non-coding RNA delivery. However, the high cytotoxicity associated with its high molecular weight has limited its application in gene delivery. To address this limitation, herein, we designed a novel delivery system using fluorine-modified polyethyleneimine (PEI) 1.8 kDa for microRNA-942-5p-sponges non-coding RNA delivery. Compared to PEI 25 kDa, this novel gene delivery system demonstrated an approximately six-fold enhancement in endocytosis capability and maintain a higher cell viability. In vivo studies also showed good biosafety and anti-tumor effects, attribute to the positive charge of PEI and the hydrophobic and oleophobic properties of the fluorine-modified group. This study provides an effective gene delivery system for non-small-cell lung cancer treatment.

Keywords: Fluorine-modified PEI; Gene delivery; NSCLC lung cancer therapy; Polyplexes.

MeSH terms

Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Fluorine
Gene Transfer Techniques
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
MicroRNAs* / genetics
Polyethyleneimine / chemistry
RNA, Untranslated
Transfection

Substances

Polyethyleneimine
Fluorine
MicroRNAs
RNA, Untranslated
MIRN942 microRNA, human