Alendronate-Conjugated Amphiphilic Hyperbranched Polymer Based on Boltorn H40 and Poly(ethylene glycol) for Bone-Targeted Drug Delivery

被引：78
作者：
Chen, Hongying [1 ]
Li, Guolin [1 ]
Chi, Huirong [1 ]
Wang, Dali [3 ]
Tu, Chunlai [3 ]
Pan, Lijie [2 ]
Zhu, Lijuan [3 ]
Qiu, Feng [3 ]
Guo, Fulin [1 ]
Zhu, Xinyuan [3 ]
机构：
[1] Harbin Med Univ, Dept Oral & Maxillofacial Surg, Affiliated Hosp 1, Harbin 150001, Peoples R China
[2] Harbin Med Univ, Dept Prevent Oral Hlth, Affiliated Hosp 1, Harbin 150001, Peoples R China
[3] Shanghai Jiao Tong Univ, State Key Lab Met Matrix Composites, Sch Chem & Chem Engn, Shanghai 200240, Peoples R China
来源：
BIOCONJUGATE CHEMISTRY | 2012年 / 23卷 / 09期
基金：
中国国家自然科学基金;
关键词：
IN-VITRO; UNIMOLECULAR MICELLES; ANTITUMOR-ACTIVITY; DESIGN; NANOPARTICLES; COPOLYMER; BISPHOSPHONATES; NANOCARRIERS; PACLITAXEL; THERAPY;
D O I：
10.1021/bc3003088
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
A novel type of alendronate(ALE)-conjugated amphiphilic hyperbranched copolymer based on a hydrophobic hyperbranched Boltorn H40 (H40) core with ALE targeting moiety and many hydrophilic poly(ethylene glycol) (PEG) arms was synthesized as a carrier for bone-targeted drug delivery. The star copolymer H40-star-PEG/ALE was characterized using nuclear magnetic resonance (NMR), Fourier transformed infrared spectroscopy (FTIR), and gel permeation chromatography (GPC) analysis. Benefiting from its highly branched structure, H40-star-PEG/ALE could form micelles in aqueous solution, which was confirmed by transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. The cytotoxicity and hemolysis of the H40-star-PEG/ALE micelles were evaluated via methylthiazoletetrazolium (MTT) assay against NIH/3T3 normal cells and red blood cell (RBC) lysis assay, respectively. As a model anticancer drug, doxorubicin (DOX) was encapsulated into the H40-star-PEG/ALE micelles. The anticancer activity of DOX-loaded micelles was evaluated by MTT assay against an HN-6 human head and neck carcinoma cell line. The strong affinity of H40-star-PEG/ALE micelles to bone was confirmed by the hydroxyapatite (HA) binding assay. These results indicate that the H40-star-PEG/ALE micelles are highly promising bone-targeted drug carriers for skeletal metastases.
引用
收藏
页码：1915 / 1924
页数：10
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