Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Sichuan University, No. 17, Block 3 Southern Renmin Road, Chengdu, 610041, China.
School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania, 15217, USA.
Pharm Res. 2018 Aug 24;35(10):196. doi: 10.1007/s11095-018-2480-8.
The aim of this study was to design hyaluronic acid (HA) layer-by-layer (LbL) nanoparticles, which carried paclitaxel (PTX) and Indocyanine green (ICG) to both tumor cells and tumor associated cells to achieve synergistic chemo-photothermal therapeutic effect.
The LbL-engineered nanoparticles (PDIH) were prepared by dopamine self-polymerization on PTX nanocrystal to form thin, surface-adherent polydopamine (PDA) films, which subsequently absorbed ICG and HA. The tumor cell and tumor associated cell targeting and antitumor efficacy of PDIH were investigated both in vitro an in vivo using 4 T1 murine mammary cancer cell lines and mice bearing orthotopic 4 T1 breast tumor.
PDIH presented a long-rod shape in TEM and showed enhanced photothermal effect and cytotoxicity upon NIR laser irradiation both in vitro and in vivo. PDIH also displayed high target ability to CD44 overexpressed tumor cells and tumor associated cells mediated by HA. In vivo antitumor study indicated that PDIH therapeutic strategy could achieve remarkable antitumor efficacy.
PDIH showed excellent tumor-targeting property and chemo-photothermal therapeutic efficacy.
本研究旨在设计透明质酸（HA）层层（LbL）纳米粒子，将紫杉醇（PTX）和吲哚菁绿（ICG）携带到肿瘤细胞和肿瘤相关细胞中，以实现协同的化疗-光热治疗效果。
通过多巴胺自聚合在 PTX 纳米晶体上形成薄的、表面附着的聚多巴胺（PDA）膜，随后吸收 ICG 和 HA，制备了 LbL 工程化纳米粒子（PDIH）。使用 4T1 鼠乳腺癌细胞系和荷原位 4T1 乳腺癌的小鼠在体外和体内研究了 PDIH 对肿瘤细胞和肿瘤相关细胞的靶向性和抗肿瘤功效。
PDIH 在 TEM 中呈现长棒状，在体外和体内的近红外激光照射下表现出增强的光热效应和细胞毒性。PDIH 还通过 HA 介导对 CD44 过表达的肿瘤细胞和肿瘤相关细胞表现出高靶向能力。体内抗肿瘤研究表明，PDIH 的治疗策略可以实现显著的抗肿瘤功效。
PDIH 表现出优异的肿瘤靶向性和化疗-光热治疗效果。
