Core–Satellite Nanomedicines for in Vivo Real-Time Monitoring of Enzyme-Activatable Drug Release by Fluorescence and Photoacoustic Dual-Modal Imaging

作者：Xianlei Li, Massimo Bottini, Luyao Zhang, Shuai Zhang, Jing Chen, Tingbin Zhang, Lu Liu, Nicola Rosato, Xibo Ma, Xinghua Shi, Yan Wu, Weisheng Guo, Xing‐Jie Liang · 发表于：ACS Nano · 年份：2018 · DOI：10.1021/acsnano.8b05136 · 被引用次数：79 · 研究领域：Nanoplatforms for cancer theranostics、Photoacoustic and Ultrasonic Imaging、Nanoparticle-Based Drug Delivery

It remains an unresolved challenge to achieve spatial and temporal monitoring of drug release from nanomedicines (NMs) in vivo, which is of crucial importance in disease treatment. To tackle this issue, we constructed core-satellite ICG/DOX@Gel-CuS NMs, which consist of gelatin (Gel) nanoparticles (NPs) with payloads of near-infrared fluorochrome indocyanine green (ICG) and chemo-drug doxorubicin (DOX) and surrounding CuS NPs. The fluorescence of ICG was initially shielded by satellite CuS NPs within the intact ICG/DOX@Gel-CuS NMs and increased in proportion to the amount of DOX released from NMs in response to enzyme-activated NMs degradation. For more comprehensive understanding of the drug-release profile, a theoretical model derived from computer simulation was employed to reconstruct the enzyme-activatable drug release of the ICG/DOX@Gel-CuS NMs, which demonstrated the underlying kinetics functional relationship between the released DOX amount and recovered ICG fluorescence intensity. The kinetics of drug release in vivo was assessed by administrating ICG/DOX@Gel-CuS NMs both locally and systemically into MDA-MB-231 tumor-bearing mice. Upon accumulation of ICG/DOX@Gel-CuS NMs in the tumor, overexpressed enzymes triggered the degradation of the gelatin scaffold as well as the release of DOX and ICG, which can be visually depicted with the ICG fluorescence signal increasing only in the tumor area by fluorescence imaging. Additionally, the photoacoustic signal from CuS NPs ...