Dual-functional liposome for tumor targeting and overcoming multidrug resistance in hepatocellular carcinoma cells

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Hepatocellular carcinoma (HCC) is a major global health concern.
• Multidrug resistance (MDR) significantly limits the efficacy of chemotherapy in HCC.
• Novel drug delivery systems are needed to overcome MDR and improve treatment outcomes.

Purpose of the Study:

• To design and evaluate a dual-functional liposome (LPG) system for targeted delivery and reversal of MDR in HCC.
• To incorporate a synthetic polymeric nano-biomaterial (Gal-P123) for enhanced targeting and drug resistance modulation.
• To investigate the therapeutic potential of mitoxantrone-loaded LPG (MX-LPG) in preclinical HCC models.

Main Methods:

• Synthesis and characterization of MX-LPG nanoparticles (size, shape, encapsulation efficiency).
• Evaluation of cytotoxicity and cellular uptake in HCC Huh-7 cells.
• Assessment of LPG's inhibitory effect on drug efflux transporters using MDCKII/BCRP cells.
• Pharmacokinetic studies in rats and antitumor activity assessment in mice bearing orthotopic HCC xenografts.

Main Results:

• MX-LPG nanoparticles were approximately 100 nm in diameter with 97.3% encapsulation efficiency.
• MX-LPG exhibited 2.3-fold higher cytotoxicity in Huh-7 cells compared to mitoxantrone (MX) alone.
• MX-LPG demonstrated a 14.9-fold increase in cellular MX accumulation in drug-resistant cells.
• In vivo studies showed prolonged circulation time, enhanced bioavailability, increased antitumor activity, and improved selectivity of MX-LPG.

Conclusions:

• Dual-functional LPG nanoparticles effectively target HCC cells and overcome MDR.
• MX-LPG represents a promising nanotherapeutic strategy for enhancing HCC treatment.
• The Gal-P123 component contributes to the targeted delivery and MDR-reversal capabilities of the liposomes.