Study on a pH-sensitive controlled release nano-drug delivery system based on gold nanorods combined with hyperthermia in the treatment of cancer in vivo

Abstract

Objective To investigate the in vivo anti-tumor effect combined with hyperthermia of a pH sensitive nano-drug delivery system based on the gold nanorods (AuNR). Methods AuNR was prepared by seed mediated growth method firstly, and then it was modified with SH-PEG2000-NH2. Finally, doxorubicin (DOX) was connected through hydrazine bond to construct the AuNR-polyethylene glycol (PEG)-DOX nano-drug delivery system with pH-sensitive controlled release effect. Ultraviolet-Visible spectroscopy (UV-Vis) and transmission electron microscope (TEM) were used to detect the characteristic absorption peaks, shape and size of AuNR, respectively. The products of each step of chemical reaction was determined by fourier transform infrared spectroscopy (FT-IR). High performance liquid chromatography (HPLC) was used for the investigation of drug loading efficiency and pH sensitive controlled release effect. The ex vitro and in vivo imaging effect of this drug delivery system was detected by X-Ray CT. And the tumor-bearing mice were randomly divided into groups to investigate the anti-tumor effect of nano-drug delivery system combined with hyperthermia in vivo. Results The prepared AuNR has stable morphology, uniform rod-like distribution, the aspect ratio was 3.6∶1.0, and the long-diameter characteristic absorption peak at -800 nm, which can be used as a near infrared (NIR) hyperthermia sensitizer for futher research. The FT-IR result showed that DOX can be connected to the carrier surface through hydrazine bond. The drug loading efficiency and encapsulation efficiency of DOX were (12.3±2.4)% and (58.3±4.7)%, respectively. When the pH of the release medium decreased from 7.4 to 5.5, the cumulative release rate of DOX increased from (14.5±2.5)% to (80.3±2.1)%, indicating that AuNR-PEG-DOX has good pH sensitivity effect. In vivo and in vitro X-Ray imaging results showed that the drug delivery system can enhance the contrast of X-Ray CT imaging, which can be used for in vivo real-time observation. And these results also can prove that the drug delivery system has good tumor accumulation ability. Anti-tumor experiments showed that the relative volume of tumor was 0.9 which had significant difference with all of the other groups, respectively, demonstrating that AuNR-PEG-DOX combined with hyperthermia could effectively inhibit the occurrence and development of tumors in vivo. Conclusion AuNR-PEG-DOX nano-drug delivery system has pH sensitive controlled release effect, X-Ray imaging enhancement and NIR hyperthermia effect, which can effectively inhibit the proliferation of tumors in vivo. Key words: Gold nanorods; PH sensitive; X-Ray imaging; Hyperthermia; Nano-drug delivery system