Glycopolymers Mediate Suicide Gene Therapy in ASGPR-Expressing Hepatocellular Carcinoma Cells in Tandem with...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Oncology

Background:

• Cationic glycopolymers are promising gene delivery agents due to biocompatibility and ASGPR targeting in hepatocellular carcinoma (HCC).
• Current synthesis methods are complex, involving solubilization and protection/deprotection steps.
• Developing efficient and simplified synthesis for targeted gene delivery is crucial for HCC treatment.

Purpose of the Study:

• To synthesize a library of well-defined cationic glycopolymers (PAMA-co-PLAMA) using ARGET ATRP.
• To evaluate their potential as an efficient gene delivery nanosystem targeting ASGPR on HCC cells.
• To assess the in vitro antitumor efficacy of the developed nanocarriers in HCC models.

Main Methods:

• Synthesis of poly(2-aminoethyl methacrylate hydrochloride-co-poly(2-lactobionamidoethyl methacrylate) (PAMA-co-PLAMA) via ARGET ATRP.
• Characterization of glycoplexes for physicochemical properties, ASGPR specificity, and transfection efficiency.
• Evaluation of HSV-TK/GCV suicide gene therapy efficacy in 2D and 3D HCC culture models, with and without docetaxel combination.

Main Results:

• Successfully synthesized well-defined PAMA-co-PLAMA glycopolymers with suitable physicochemical properties.
• Achieved high ASGPR specificity and efficient gene transfection in HCC cells.
• Demonstrated significant antitumor activity in HCC models using HSV-TK/GCV gene therapy, enhanced by docetaxel.

Conclusions:

• Primary-amine polymethacrylate-containing-glycopolymers are effective HCC-targeted suicide gene delivery nanosystems.
• The developed nanocarriers show potential for efficient and specific gene therapy in HCC.
• Combined therapeutic strategies, including gene therapy and chemotherapy, enhance antitumor efficacy for HCC treatment.