Aptamer and Peptide-Modified Lipid-Based Drug Delivery Systems in Application of Combined Sequential Therapy of Hepatocellular Carcinoma
Jianghong Lv, Meng Tingting, Yingping Zeng, Yu Tong, Lanxia Zhao, Liu Jingwen, Zhou Wentao, Chen Pengbo, Hong Yuan, Fuqiang Hu
Abstract
Hepatocellular carcinoma (HCC) is known as the most common malignancy of the hepatobiliary system with a continued increase in incidence but limited therapeutic options. Nanomedicine has provided a promising strategy through engineered nanocarriers that are capable of targeting therapeutic agents specifically to tumor cells. In this research, two aptamer/peptide-modified lipid-based drug delivery systems (A54-PEG-SLN/OXA and A15-PEG-SLN/SAL) were developed as a sequential therapeutic strategy to conquer specific hepatocellular carcinoma. The nanomedicine A54-PEG-SLN/OXA was able to target specific hepatocellular carcinoma cell BEL-7402 and exhibited a strong targeting ability and antitumor efficiency both in vitro and in vivo. The A15-PEG-SLN/SAL could target and penetrate deeply to the spheroid composed of CD133+ cancer cells. In the study of developing a sequential therapeutic strategy, we demonstrated that A54-PEG-SLN/OXA could kill tumor cells and expose CD133+ cancer cells. After the administration of A15-PEG-SLN/SAL, the growth of the tumors was significantly inhibited. In conclusion, the aptamer/peptide-modified lipid-based drug delivery systems, A54-PEG-SLN/OXA and A15-PEG-SLN/SAL, could specifically target carcinoma cells and had an evident antitumor effect when administrated sequentially.