TY - JOUR AU - Zhang Bing-bing AU - Chen Xiao-jie AU - Fan Xu-dong AU - Zhu Jing-jing AU - Wei Ying-hui AU - Zheng Hang-sheng AU - Zheng Hong-yue AU - Wang Bin-hui AU - Piao Ji-gang AU - Li Fan-zhu PY - 2021 TI - Lipid/PAA-coated mesoporous silica nanoparticles for dual-pH-responsive codelivery of arsenic trioxide/paclitaxel against breast cancer cells JF - Acta Pharmacologica Sinica; Vol 42, No 5 (May 2021): Acta Pharmacologica Sinica Y2 - 2021 KW - N2 - 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 stimulus- responsive 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-PTX/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 (pH e = 6.5, pH endo = 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-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy. UR - http://www.chinaphar.com/article/view/10325