Lipid/PAA-coated mesoporous silica nanoparticles for dual-pH-responsive codelivery of arsenic trioxide/paclitaxel against breast cancer cells

• 作者: Bing-bing Zhang Xiao-jie Chen Xu-dong Fan Jing-jing Zhu Ying-hui Wei Hang-sheng Zheng Hong-yue Zheng Bin-hui Wang Ji-gang Piao Fan-zhu Li
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2021,（5）
• 所属期刊栏目: Pharmaceutics
• 页码范围: 832-842
• 页数: 11页
• 语种: 英文

摘要

Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy.In particular,the distinction of tumor microenvironment and normal tissues is often used in stimulusresponsive drug delivery systems for controlled release of therapeutic agents at target sites.In this study,we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA),and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PrX/ATO).Tumor-targeting peptide F56 was used to modify MSNs,which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis.PAA-and PSL-coated nanoparticles were characterized by TGA,TEM,FT-IR,and DLS.The drug-loaded nanoparticles displayed a dual-pH-responsive (piHe =65,pHendo =5.0) and sequential drug release profile.PTX within PSL was preferentially released at pH=6.5,whereas ATO was mainly released at pH =5.0.Drug-free carriers showed low cytotoxicity toward MCF-7 cells,but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells,showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs.Furthermore,the extracellular release of PTX caused an expansion of the interstitial space,allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect.As a result,FPL-PMSN-PrX/ATO exhibited improved in vivo circulation time,tumor-targeted delivery,and overall therapeutic efficacy.