Nanocomposite hydrogel incorporating gold nanorods and paclitaxel-loaded chitosan micelles for combination photothermal–chemotherapy

• Published in: International journal of pharmaceutics Vol. 497; no. 1-2; pp. 210 - 221
• Main Authors: Zhang, Nan, Xu, Xuefan, Zhang, Xue, Qu, Ding, Xue, Lingjing, Mo, Ran, Zhang, Can
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.01.2016
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Chemotherapy; Chitosan - chemistry; Chitosan micelles; Combination therapy; Combined Modality Therapy; Drug Carriers; Drug Stability; Gold - administration & dosage; Gold - chemistry; Gold nanorod; Hydrogels - administration & dosage; Hydrogels - chemistry; Hyperthermia, Induced; Injections, Intralesional; Laser Therapy - methods; Male; Mice; Micelles; Nanocomposites - administration & dosage; Nanocomposites - chemistry; Nanotubes - chemistry; Neoplasms - therapy; Paclitaxel - administration & dosage; Paclitaxel - pharmacology; Phototherapy; Photothermal therapy; Xenograft Model Antitumor Assays; Photothermal therapy; Chemotherapy; Gold nanorod; Combination therapy; Chitosan micelles
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2015.11.032

[Display omitted] Development of combination photothermal–chemotherapy platform is of great interest for enhancing antitumor efficacy and inhibiting tumor recurrence, which supports selective and dose-controlled delivery of heat and anticancer drugs to tumor. Here, an injectable nanocomposite hydrogel incorporating PEGylated gold nanorods (GNRs) and paclitaxel-loaded chitosan polymeric micelles (PTX-M) is developed in pursuit of improved local tumor control. After intratumoral injection, both GNRs and PTX-M can be simultaneously delivered and immobilized in the tumor tissue by the thermo-sensitive hydrogel matrix. Exposure to the laser irradiation induces the GNR-mediated photothermal damage confined to the tumor with sparing the surrounding normal tissue. Synergistically, the co-delivered PTX-M shows prolonged tumor retention with the sustained release of anticancer drug to efficiently kill the residual tumor cells that evade the photothermal ablation due to the heterogeneous heating in the tumor region. This combination photothermal–chemotherapy presents superior effects on suppressing the tumor recurrence and prolonging the survival in the Heps-bearing mice, compared to the photothermal therapy alone.