Novel Nanotechnology Approaches to Overcome Drug Resistance in the Treatment of Hepatocellular Carcinoma: Glypican 3 as a Useful Target for Innovative Therapies

Abstract

Hepatocellular carcinoma (HCC) is the second most lethal tumor, with a 5-year survival rate of 18%. Early stage HCC is potentially treatable by therapies with curative intent, whereas chemoembolization/radioembolization and systemic therapies are the only therapeutic options for intermediate or advanced HCC. Drug resistance is a critical obstacle in the treatment of HCC that could be overcome by the use of targeted nanoparticle-based therapies directed towards specific tumor-associated antigens (TAAs) to improve drug delivery. Glypican 3 (GPC3) is a member of the glypican family, heparan sulfate proteoglycans bound to the cell surface via a glycosylphosphatidylinositol anchor. The high levels of GPC3 detected in HCC and the absence or very low levels in normal and non-malignant liver make GPC3 a promising TAA candidate for targeted nanoparticle-based therapies. The use of nanoparticles conjugated with anti-GPC3 agents may improve drug delivery, leading to a reduction in severe side effects caused by chemotherapy and increased drug release at the tumor site. In this review, we describe the main clinical features of HCC and the common treatment approaches. We propose the proteoglycan GPC3 as a useful TAA for targeted therapies. Finally, we describe nanotechnology approaches for anti-GPC3 drug delivery systems based on NPs for HCC treatment.

Navigating the Future: Nanotechnological Strategies for Tackling Hepatocellular Carcinoma

“…The conventional methods for detecting and treating HCC is less effective when compared to modern practices of nanotechnology since the particles have high responsiveness, reduces drug-induced toxicity and it can also be fused with 'theranostics' [9]. One of the foremost challenges in the domain of oncological treatment concerns the phenomenon of drug non-responsiveness, which can be triumphed over through the application of nanoparticle-based therapies that are specifically directed towards tumour-associated antigens (TAAs) in order to enhance drug delivery [10]. Nanotechnological activities helps to understand life processes at a more molecular-scale domain [6].…”

Activated Hepatic Stellate Cells in Hepatocellular Carcinoma: Their Role as a Potential Target for Future Therapies

“…Activated HSCs produce more ECM, leading to chronic fibrosis and cirrhosis and eventually to HCC ( Figure 1 ) [ 6 ]. Despite significant advances in the treatment of HCC, drug-resistance is a critical obstacle [ 11 ], and the 5-year survival rate is low (5–14%) [ 12 ], but survival rates of greater than 20% have been reached in some regions [ 13 ]. Therefore, there is a potential to increase survival rates.…”

Strategies and Recent Advances on Improving Efficient Antitumor of Lenvatinib Based on Nanoparticle Delivery System

“…(40% overexpression rate), lectins, glypican-3 (GPC3), 90 folate receptor (approximately 40%) 91 and epithelial cell adhesion molecule (EpCAM). [92][93][94] Active targeting is a therapeutic strategy that effectively controls biodistribution and maximizes the accumulation of agents at the tumor cells with minimum toxicity, causing improved efficiency and patient compliance.…”