Hyaluronic acid-coated poly(β-amino) ester nanoparticles as carrier of doxorubicin for overcoming drug resistance in breast cancer cells
Hyaluronic acid-coated poly(β-amino) ester nanoparticles as carrier of doxorubicin for overcoming drug resistance in breast cancer cells
复制标题
透明质酸包被的聚（b-氨基）酯纳米颗粒作为阿霉素载体克服乳腺癌细胞的耐药性
DOI：
10.1039/c6ra03997a
复制
发表时间：
2016-01-01
期刊：
影响因子：
3.9
通讯作者：
Wang, Yinsong
中科院分区：
文献类型：
--
作者：
An, Tong;Zhang, Cong;Wang, Yinsong
耐药性是化疗药物临床应用面临的主要挑战。本研究设计了一种以透明质酸（HA）为壳、聚（β-氨基）酯（PBAE）为核的纳米粒体系，作为临床常用化疗药物阿霉素（DOX）的载体，以克服乳腺癌细胞的耐药性。采用O/W乳化溶剂挥发法制备了DOX负载PBAE（PBAE/DOX）纳米粒子，并通过电荷相互作用对HA进行表面包覆。HA包覆的PBAE/DOX（HA/PBAE/DOX）纳米粒具有典型的“核-壳”结构，粒径约为185.0 nm，具有明显的pH响应性体外释药特性。与游离DOX和PBAE/DOX纳米粒相比，HA/PBAE/DOX纳米粒对人乳腺癌MCF-7/ADR耐药细胞具有更强的细胞毒性、细胞凋亡和S期细胞阻滞作用。由于HA是CD 44的天然配体，HA/PBAE/DOX纳米粒可通过CD 44介导的内吞作用进入MCF-7/ADR细胞，有效地避免了P-gp的外排作用，促进了DOX在细胞内的蓄积。因此，HA/PBAE纳米粒系统可作为化疗药物的潜在载体，用于逆转肿瘤的耐药性。
Drug resistance is a major challenge for the clinical application of chemotherapeutic drugs. In this study, a nanoparticle system containing hyaluronic acid (HA) shell and poly(beta-amino) ester (PBAE) core was designed as a carrier for doxorubicin (DOX), a commonly used chemotherapeutic drug in clinical, to overcome the drug resistance in breast cancer cells. DOX-loaded PBAE (PBAE/DOX) nanoparticles were firstly prepared using the O/W emulsion solvent evaporation method, and followed by the surface coating of HA via charge interaction. HA-coated PBAE/DOX (HA/PBAE/DOX) nanoparticles had a classic "core-shell" structure with a size of 185.0 nm and displayed obvious pH-responsive in vitro drug release property. Compared to free DOX and PBAE/DOX nanoparticles, HA/PBAE/DOX nanoparticles exhibited the enhanced cytotoxicity, cell apoptosis and S-phase cell cycle arrest in drug-resistant human breast cancer MCF-7/ADR cells, in which P-glycoprotein (P-gp), a typical and well-known mediator of cancer drug resistance, and CD44, a cell-surface adhesion receptor, were over-expressed. As HA was a natural ligand for CD44, HA/PBAE/DOX nanoparticles could enter MCF-7/ADR cells via CD44-mediated endocytosis, thus efficiently avoided the efflux effect of P-gp and improved the cellular accumulation of DOX. In summary, HA/PBAE nanoparticle system could be used as a potential carrier of chemotherapeutic drugs for the reversal of drug resistance in cancers.