A targeted and redox/pH-responsive chitosan oligosaccharide derivatives based nanohybrids for overcoming multidrug resistance of breast cancer cells

作者

Jia, LJ; Li, ZY; Zheng, DD; Li, ZY; Zhao, ZX

作者单位

[Jia, Lejiao] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Pharm, Jinan 250013, Peoples R China; [Li, Zhenyu] Shandong First Med Univ, Dept Pharm, Shandong Prov Hosp, Jinan 250021, Peoples R China; [Zheng, Dandan; Li, Zhiying; Zhao, Zhongxi] Shandong Univ, Cheeloo Coll Med, Sch Pharmaceut Sci, Jinan 250012, Peoples R China

摘要

A novel folic acid mediated chitosan oligosaccharide-grafted disulfide-containing polyethylenimine copolymer-based silica nanohybrids were fabricated for co-delivering paclitaxel and P-shRNA. These nanoparticles could efficiently protect P-shRNA against degradation, and exhibited well redox-responsive P-shRNA release and pH-responsive drug release behaviors. Folic acid as the targeting head, could improve cellular uptake of nanoparticles by multidrug-resistant breast cancer cells. Moreover, these nanoparticles showed excellent delivery P-shRNA into cells and displayed high gene silencing efficiency at the targeted mRNAs to downregulate the expression of P-gp which induced up to 63% decrease. Finally, nanoparticles could completely reverse the resistance of breast cancer cells to paclitaxel and the resistance reversion index was 50.59. These results suggested that our nanoparticles could efficiently co-deliver paclitaxel and P-shRNA into cancer cells to exert its synergistic antitumor effect, and opened up a new avenue for overcoming multidrug resistance.

关键词

ACID MODIFIED CHITOSAN; INTRACELLULAR DRUG; DELIVERY; IMMUNOTHERAPY; CHEMOTHERAPY; APOPTOSIS; MICELLES

基本信息

所属机构:

归属医师: 李震宇

PMID：33142574

UT：000582801500027

刊名:CARBOHYDRATE POLYMERS

年，卷(期):2021年251卷

DOI：10.1016/j.carbpol.2020.117008

附件： other

收录: SCIE