Enhanced Delivery of Thermoresponsive Polymer-Based Medicine into Tumors by Using Heat Produced from Gold Nanorods Irradiated with Near-Infrared Light

Cancers

Kohei Sano¹  Toshie Tanaka¹  Toshihide Yamasaki¹  Yoshie Haratake¹  Tomono Nagayama¹  Tatsuya Mizukami¹  Takahiro Mukai¹  Masayuki Munekane¹  Yumi Ishida¹ 

[1] Laboratory of Biophysical Chemistry, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan;

关键词: thermoresponsive polymer;    polyoxazoline;    gold nanorod;    near-infrared light;    drug delivery system;   

DOI  :  10.3390/cancers13195005

来源: DOAJ

【 摘 要 】

The aim of this study was to establish a drug delivery system (DDS) for marked therapy of tumors using a thermoresponsive polymer, polyoxazoline (POZ). The effectiveness of the following was investigated: (i) the delivery of gold nanorods (GNRs) to tumor tissues, (ii) heat production of GNR upon irradiation with near-infrared (NIR) light, and (iii) high accumulation of an intravenously injected radiolabeled POZ as a drug carrier in tumors by sensing heat produced by GNRs. When the GNR solution was irradiated with NIR light (808 nm), the solution temperature was increased both in a GNR-concentration-dependent manner and in a light-dose-dependent manner. POZ, with a lower critical solution temperature of 38 °C, was aggregated depending on the heat produced by the GNR irradiated by NIR light. When it was intratumorally pre-injected into colon26-tumor-bearing mice, followed by NIR light irradiation (GNR+/Light+ group), the tumor surface temperature increased to approximately 42 °C within 5 min. Fifteen minutes after irradiation with NIR light, indium-111 (¹¹¹In)-labeled POZ was intravenously injected into tumor-bearing mice, and the radioactivity distribution was evaluated. The accumulation of POZ in the tumor was significantly (approximately 4-fold) higher than that in the control groups (GNR+/without NIR light irradiation (Light–), without injection of GNR (GNR–)/Light+, and GNR–/Light– groups). Furthermore, an in vivo confocal fluorescence microscopy study, using fluorescence-labeled POZ, revealed that uptake of POZ by the tumor could be attributed to the heat produced by GNR. In conclusion, we successfully established a novel DDS in which POZ could be efficiently delivered into tumors by using the heat produced by GNR irradiated with NIR light.

【 授权许可】

Unknown