화학공학소재연구정보센터
Biomacromolecules, Vol.18, No.12, 3869-3880, 2017
Doxorubicin-Loaded Unimolecular Micelle-Stabilized Gold Nanoparticles as a Theranostic Nanoplatform for Tumor-Targeted Chemotherapy and Computed Tomography Imaging
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.