Aptamer and Peptide-Modified Lipid-Based Drug Delivery Systems in Application of Combined Sequential Therapy of Hepatocellular Carcinoma.

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.