文献类型：期刊文献

英文题名：Application of mPEG-CS-cRGD/Bmi-1RNAi-PTX nanoparticles in suppression of laryngeal cancer by targeting cancer stem cells

作者：Xu, Xiaoyan[1,2];Zhou, Tianhao[1,2];Wei, Xudong[1,2,3,5];Jiang, Xuelian[1,3];Cao, Jiyan[1,4]

第一作者：徐晓艳;徐小艳;Xu, Xiaoyan

通信作者：Wei, XD[1]

机构：[1]Gansu Prov Hosp, Dept ENT, Lanzhou, Peoples R China;[2]Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou, Peoples R China;[3]Lanzhou Univ, Sch Clin Med 1, Lanzhou, Peoples R China;[4]Ningxia Med Univ, Dept Clin Med, Yinchuan, Peoples R China;[5]Gansu Univ Chinese Med, Lanzhou Univ, Gansu Prov Hosp, Sch Clin Med 1,Dept ENT, Lanzhou 730000, Peoples R China

第一机构：Gansu Prov Hosp, Dept ENT, Lanzhou, Peoples R China

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Lanzhou Univ, Gansu Prov Hosp, Sch Clin Med 1,Dept ENT, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2023

卷号：30

期号：1

外文期刊名：DRUG DELIVERY

收录：;Scopus(收录号：2-s2.0-85148653821);WOS:【SCI-EXPANDED(收录号:WOS:000934538100001)】；

基金：This study was supported by National Natural Science Foundation of China (No. 81860475); Key projects of national scientific research project cultivation plan of Gansu Provincial Hospital (No. 19SYPYA-13); Project of natural Science Foundation of Gansu Province (No. 20JR10RA377); Lanzhou Talents Innovation and entrepreneurship Project (No. 2021-RC-129); Gansu Excellent Young Talents Project in Health Field (GSWSQN2021-002). We acknowledge and appreciate Dr. Zuoren Yu, Professor of Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, for his valuable efforts and comments on this paper. In the other hand, we acknowledge and appreciate our colleagues for their valuable efforts on this paper.

语种：英文

外文关键词：laryngeal cancer; cancer stem cells; nanoparticles; Bmi-1; cRGD peptide; paclitaxel

摘要：Although surgery-based comprehensive therapy is becoming the main approach to treat laryngeal cancer, recurrence, metastasis, radiotherapy resistance and chemotherapy tolerance are still the main causes of death in patients. Targeted inhibition of laryngeal cancer stem cells has been considered as the consensus to cure laryngeal cancer. Our previous study has confirmed proto-oncogene Bmi-1 as a key regulator for self-renewal of laryngeal cancer stem cells. Targeted knockdown of Bmi-1 gene effectively inhibited the self-renewal and differentiation of laryngeal cancer stem cells, leading to the promoted sensitivity to chemotherapy including paclitaxel. However, due to off-target effects and quick degradation of the naked Bmi-1-RNAi small RNA oligo by nuclease in body fluids, it is urgently needed to develop a tumor-targeted delivery system with a protective shell. In this study, we designed and synthesized cRGD peptide-modified chitosan-polyethylene glycol slow-release nanoparticles (mPEG-CS-cRGD/Bmi-1RNAi-PTX) containing Bmi-1RNAi siRNA oligo and paclitaxel, which showed spherical in shape, 200 nm diameter in size, low cytotoxicity, strong DNA wrapping, resistance to nuclease degradation and high transfection efficiency to cells. Functional analysis indicated significant suppression of cell proliferation and migration and induction of apoptosis by the nanocomplex in laryngeal cancer cells in vitro. By application to the mouse model with laryngeal cancer, the nanocomplex inhibited tumor growth significantly in vivo. In addition, cRGD peptide, paclitaxel and Bmi-1 siRNA in the nanoparticles showed synergistic effects to suppress laryngeal cancer stem cells. In conclusion, this study not only developed a laryngeal tumor-targeted chemotherapeutic system, but also demonstrated a Bmi-1 RNAi-based chemotherapeutic strategy to inhibit cancer stem cells, having strong potential to treat laryngeal cancer patients suffering therapy resistance and/or tumor recurrence.