The role of multi-functional delivery system based on gold nanomaterials in the treatment of liver cancer

Abstract

Objective To explore the effect of multi-functional delivery system based on gold nanomaterials in the treatment of liver cancer. Methods Gold nanorods (AuNR) with near infrared (NIR) thermotherapy characteristics were prepared by gold seed growth method; Mercaptoacetic acid (SH)-polyethyleneimine (PEI) was prepared by reaction of thioglycolic acid with PEI; AuNR were chemically modified with SH-PEI and SH-PEG2000-NH2; a certain amount of AS1411 was chemically bonded. To the AuNR vector. The clinically used anticancer drug Doxorubicin (DOX) is linked to the amino terminus of SH-PEI by a hydrazone bond (pH sensitive). Human hepatoma HepG2 cells were prepared as an in vitro cell model and a nude mouse liver cancer model, and in vitro drug tests and drug distribution in vivo were observed. Results The particle size of the drug-loaded nanoparticles was <200 nm, and the zeta potential was stable at 35-190 mV. Except for the AuNR-PEI/PEG-DOX-AS1411 nanoparticles with a mass ratio of 3/25, the PDI of other nanoparticles was 0.2, indicating the particle size. The distribution is more uniform. The AuNR-PEI/PEG-DOX-AS1411 nanoparticles have a drug loading of 5%-25% and an encapsulation efficiency of 50%-70%. Aunr-pei/peg-dox-as1411 nanoparticles presented regular rod-like shape, with a aspect ratio of 3.6 and a uniform distribution. The Zeta potential was -16.7 mV and the drug load was 8.2%. Further investigation by dynamic dialysis showed that the release of DOX showed pH-responsiveness. When the pH of the release medium decreased from 7.4 to 6.5, the drug release increased slowly. When the pH of the release medium decreased to 5.5, the drug release increased rapidly. The cumulative release of DOX at the 24 h time point was 56.7%. Free Cy5.5 was rapidly cleared in tumor-bearing mice. After 6 hours of injection, the red fluorescent signal was weak and completely cleared after 24 hours. The clearance time of AuNR-PEI/PEG-DOX-AS1411 nanoparticles in tumor-bearing mice was significantly delayed. Some nanoparticles were distributed in the liver 6h after injection, 24h in liver, spleen and lung sputum, and a little in tumor and kidney tissues. . The nanoparticles began to accumulate in the tumor tissue after 6 hours of tail vein injection. After 24 hours, the nanoparticles were mainly distributed in the tumor, and a small part was distributed in the liver. After dissecting the mice, it was found that the nanoparticles were mainly distributed in the tumor tissues and distributed less in the liver. Conclusion AuNR-PEI/PEG-DOX-AS1411 nanoparticles can effectively support the anti-tumor drug DOX, which can inhibit the migration of liver cancer cells and exhibit good liver cancer targeting. Key words: Liver cancer; Gold nano; Delivery system