期刊
ACS APPLIED MATERIALS & INTERFACES
卷 10, 期 45, 页码 38700-38714出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b11349
关键词
prodrug nanomicelle; esterase-sensitive; carboxylated indocyanine green; tumor-specific imaging; cancer photothermal-chemotherapy
资金
- National Major Scientific and Technological Special Project for Significant New Drugs Development [2016ZX09101031]
- National Natural Science Foundation of China [81502680, 81102398, 31872756]
- Graduate Cultivation Innovative Project of Jiangsu Province [SJLX16_0239]
- National Foundation for Fostering Talents of Basic Science [J1030830]
- Jiangsu Six Talent Peaks Program [JY-079]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Double First-Class Innovation Team Project of China Pharmaceutical University [CPU2018GY23, CPU2018GY26]
Photothermal therapy is a promising approach for antitumor application although regrettably restricted by available photothermal agents. Physical entrapment of organic near-infrared dyes into nanosystems was extensively studied to reverse the dilemma. However, problems still remained, such as drug bursting and leakage. We developed here an amphiphilic prodrug conjugate by chemically modifying indocyanine green derivative (ICG-COOH) and paclitaxel (PTX) to hyaluronic acid (HA) backbone for integration of photothermal-chemotherapy and specific tumor imaging. The prepared ICG-HA-PTX conjugates could self-assemble into nanomicelles to improve the stability and reduce systemic toxicity of the therapeutic agents. The high local concentration of ICG-COOH in nanomicelles resulted in fluorescence self-quenching, leading to no fluorescence signal being detected in circulation. When the nanomicelles reached the tumor site via electron paramagnetic resonance effect and HA-mediated active targeting, the overexpressed esterase in tumor cells ruptured the ester linkage between drugs and HA, achieving tumor-targeted therapy and specific imaging. A series of in vitro and in vivo experiments demonstrated that the easily prepared ICG-HA-PTX nanomicelles with high stability, smart release behavior, and excellent tumor targeting ability showed formidable synergy in tumor inhibition, which provided new thoughts in developing an organic near-infrared-dye-based multifunctional delivery system for tumor theranostics.
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