Acid-Responsive Polymeric Doxorubicin Prodrug Nanoparticles Encapsulating a Near-Infrared Dye for Combined Photothermal-Chemotherapy

作者：Zhang, Yuanyuan; Teh, Cathleen; Li, Menghuan; Ang, Chung Yen; Tan, Si Yu; Qu, Qiuyu; Korzh, Vladimir^*; Zhao, Yanli^*

来源：Chemistry of Materials, 2016, 28(19): 7039-7050.

DOI：10.1021/acs.chemmater.6b02896

• ANTICANCER DRUG-DELIVERY
• CANCER COMBINATION THERAPY
• PHOTODYNAMIC THERAPY
• TRANSGENIC ZEBRAFISH
• ACTIVATABLE PRODRUG
• LIVER TUMORIGENESIS
• CARBON NANOTUBES
• IN-VITRO
• MICELLES
• PH

Combination therapy with high spatial and temporal resolution is highly promising for efficient medical treatment of cancer. In this study, doxorubicin (DOX) conjugated amphiphilic block copolymer with a terminal folic acid moiety was prepared, which could self-assemble into nanoparticles by encapsulating organic near-infrared (NIR) absorbing dye IR825 for combined photothermal-chemotherapy. The resulting PDOX/IR825 nanoparticles showed excellent colloidal stability and monodispersity in aqueous solution. Specifically, the conjugated DOX could be released quickly in weak acidic environment for chemotherapy due to the cleavage of acid-labile hydrazone bond. Meanwhile, the encapsulated dye could convert the NIR light energy into heat with high efficiency, which makes the self-assembled nanoparticles an effective platform for photothermal therapy. Confocal microscopy observations and flow cytometry analysis confirmed that the PDOX/IR825 nanoparticles could be efficiently endocytosed by HeLa cells and deliver DOX into the nuclei of cancer cells. The in vitro cell viability assays indicated that both DOX-sensitive HeLa cells and DOX-resistant A2780/DOXR cells were completely killed by the treatment of PDOX/IR825 under NIR light irradiation. Significant tumor regression was also observed in the zebrafish liver hyperplasia model upon combinational therapy provided from the PDOX/IR825 nanoparticles. Hence, the PDOX/IR825 nanoparticles exhibited a great potential in site-specific combined photothermal-chemotherapy of tumor.

• 出版日期2016-10-11
• 单位南阳理工学院; 淮海工学院