Dually folate/CD44 receptor-targeted self-assembled hyaluronic acid nanoparticles for dual-drug delivery and combination cancer therapy

被引：45

作者：

Song, Liang ^{[1
,2
]}

Pan, Zhou ^{[1
,2
]}

Zhang, Huabing ^{[1
,2
]}

Li, Yanxiu ^{[1
,2
]}

Zhang, Yinying ^{[1
,2
]}

Lin, Jinyan ^{[1
,2
,3
]}

Su, Guanghao ^{[4
]}

Ye, Shefang ^{[1
,2
]}

Xie, Liya ^{[5
]}

Li, Yang ^{[1
,2
]}

Hou, Zhenqing ^{[1
,2
]}

机构：

[1] Xiamen Univ, Coll Mat, Dept Biomat, Key Lab Biomed Engn Fujian Prov, Xiamen 361005, Peoples R China

[2] Xiamen Univ, Coll Mat, Dept Biomat, Res Ctr Biomed Engn Xiamen, Xiamen 361005, Peoples R China

[3] Xiamen Univ, Dept Chem, Coll Chem & Chem Engn, State Key Lab Phys Chem Solid Surface, Xiamen 361005, Peoples R China

[4] Soochow Univ, Childrens Hosp, Suzhou 215025, Peoples R China

[5] Xiamen Univ, Affiliated Hosp 1, Xiamen 361002, Peoples R China

来源：

JOURNAL OF MATERIALS CHEMISTRY B | 2017年 / 5卷 / 33期

基金：

中国博士后科学基金;

关键词：

COLLAGEN-INDUCED ARTHRITIS; MULTIDRUG-RESISTANCE; METHOTREXATE; CURCUMIN; PRODRUG; DOXORUBICIN; RELEASE; NANOTECHNOLOGY; STRATEGY; EFFICACY;

D O I：

10.1039/c7tb01548h

中图分类号：

TB3 [工程材料学]; R318.08 [生物材料学];

学科分类号：

0805 ; 080501 ; 080502 ;

摘要：

Nanoparticles (NPs) functionalized with targeting ligands have shown promise, but are still limited by their nonspecific uptake by certain healthy tissues and cells that express low or even comparable levels of receptors. To increase their accumulation at tumor sites while decreasing the unintended toxicity, a possible solution is the involvement of two separate tumor-specific ligands in the localization. In this study, a dual tumor-targeting drug-loaded NP system was self-assembled by the amphiphilic conjugate of methotrexate-hyaluronic acid-octadecylamine (MTX-HA-OCA) with curcumin (CUR) encapsulated within the hydrophobic core (designated as MTX-HA-OCA/CUR NPs). The advantages of this nanosystem are that the anticancer drug MTX can be utilized as a tumor-targeting ligand toward folate receptors due to its structural similarity to folic acid (FA), and HA can serve as another tumor-targeting ligand toward CD44 receptors. The MTX-HA-OCA/CUR NPs are similar to 70 nm in diameter and have sustained/controlled drug release behavior. An in vitro cellular uptake and competition inhibition study exhibited that MTX-HA-OCA/CUR NPs could significantly enhance the internalization efficiency in HeLa cells via folate/CD44 receptor-mediated endocytosis as compared to HA-OCA/CUR NPs. More importantly, the in vitro cytotoxicity of MTX-HA-OCA/CUR NPs was significantly enhanced as compared to those of the HA-OCA/CUR NPs, both free drugs, and individual free drug. Furthermore, the real-time in vivo and ex vivo fluorescence imaging of HeLa tumor-bearing mice showed that MTX-HA-OCA/CUR NPs could more efficiently enhance their accumulation and improve the penetration at the tumor site as compared to HA-OCA/CUR NPs. Therefore, these dually folate/CD44 receptor-targeted self-assembled HA NPs for the co-delivery of both anticancer drugs might provide a promising strategy for dual-targeted combination cancer therapy.

引用

页码：6835 / 6846

页数：12