Hepatocellular carcinoma cell-specific peptide ligand for targeted drug delivery

Area of Science:

• Oncology
• Molecular Biology
• Biotechnology

Background:

• Hepatocellular carcinoma (HCC) is a major global health concern, ranking as the fourth leading cause of cancer mortality worldwide.
• Advancements in molecular oncology are crucial for developing novel and effective HCC treatment strategies.

Purpose of the Study:

• To identify and characterize a novel peptide with specific binding affinity for hepatocellular carcinoma cells.
• To evaluate the potential of this peptide as a targeted delivery agent for HCC therapy.

Main Methods:

• Phage display was employed to discover a peptide (SP94) that specifically binds to HCC cells.
• In vitro assays (ELISA, flow cytometry) and in vivo studies in mice bearing HCC xenografts were conducted to assess binding and homing capabilities.
• Immunohistochemical staining and analysis of patient surgical specimens were performed to validate tumor specificity.
• SP94 was conjugated with liposomal doxorubicin to create a targeted drug delivery system.

Main Results:

• The phage clone PC94 demonstrated specific binding to HCC cell lines in vitro.
• In vivo, PC94 exhibited specific homing to tumor tissues in mice, with no significant accumulation in normal organs.
• The homing ability was confirmed to be competitively inhibited by the synthetic SP94 peptide.
• SP94 recognized tumor tissue in 61.3% of HCC patient surgical specimens.
• The SP94-doxorubicin conjugate enhanced therapeutic efficacy by promoting tumor apoptosis and reducing angiogenesis in HCC xenografts.

Conclusions:

• SP94 is a novel peptide with high specificity for hepatocellular carcinoma cells and tissues.
• SP94 shows significant potential as a targeting moiety for developing advanced drug delivery systems in HCC treatment.
• Targeted delivery using SP94 may improve systemic therapy outcomes for patients with advanced HCC.