Doxorubicin-Loaded Unimolecular Micelle-Stabilized Gold Nanoparticles as a Theranostic Nanoplatform for Tumor-Targeted Chemotherapy and Computed Tomography Imaging

被引:55
作者
Lin, Wenjing [1 ,2 ]
Zhang, Xiaofang [1 ]
Qian, Long [3 ,4 ]
Yao, Na [1 ]
Pan, Ya [1 ]
Zhang, Lijuan [1 ]
机构
[1] South China Univ Technol, Sch Chem & Chem Engn, Guangzhou 510640, Guangdong, Peoples R China
[2] Guangdong Univ Technol, Sch Chem Engn & Light Ind, Guangzhou 510006, Guangdong, Peoples R China
[3] NYU, Dept Biol, New York, NY 10003 USA
[4] NYU, Ctr Genom & Syst Biol, 550 1St Ave, New York, NY 10003 USA
基金
中国国家自然科学基金;
关键词
NEUROENDOCRINE CANCER-THERAPY; AMPHIPHILIC BLOCK-COPOLYMER; ANTICANCER DRUG-DELIVERY; PH-SENSITIVE MICELLES; POLYMERIC MICELLES; CONTRAST AGENT; BLOOD-POOL; RELEASE; PENETRATION; CONTAINERS;
D O I
10.1021/acs.biomac.7b00810
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Current research is mainly trending toward addressing the development of multifunctional nanocarriers that could precisely reach disease sites, release drugs in a controlled-manner, and act as an imaging agent for both diagnosis and targeted therapy. In this study, a pH-sensitive theranostic nanoplatform as a promising dual-functional nanovector for tumor therapy and computed tomography (CT) imaging was developed. The 21-arm star-like triblock polymer of beta-cyclodextrin-{poly(epsilon-caprolactone)-poly(2-aminoethyl methacrylate)-poly[poly(ethylene glycol) methyl ether methacrylate]}(21) [beta-CD-(PCL-PAEMA-PPEGMA)(21)] with stable unimolecular micelles formed in aqueous solution was first synthesized by combined ROP with ARGET ATRP techniques and then was used as a template for fabricating gold nanoparticles (AuNPs) with uniform sizes and excellent colloidal stability in situ followed by the encapsulation of doxorubicin (DOX) with maximum entrapment efficiency up to 60% to generate the final product beta-CD-(PCL-PAEMA-PPEGMA)(21)/AuNPs/DOX. Furthermore, dissipative particle dynamics (DPD) simulations revealed further details of the formation process of unimolecular micelles and the morphologies and distributions of AuNPs and DOX. Almost 80% of DOX was released in 120 h in an acidic tumoral environment in an in vitro drug release experiment, and the experiments both in vitro and in vivo demonstrated the fact that beta-CD-(PCL-PAEMA-PPEGMA)21/AuNPs/DOX exhibited similar antitumor efficacy to free DOX and effective CT imaging performance. Therefore, we believe this structurally stable unimolecular micelle-based nanoplatform synergistically integrated with anticancer drug delivery and CT imaging capabilities hold great promise for future cancer theranostics.
引用
收藏
页码:3869 / 3880
页数:12
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