Drug delivery strategy in hepatocellular carcinoma therapy

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high rates of recurrence and death. Surgical resection and ablation therapy have limited efficacy for patients with advanced HCC and poor liver function, so pharmacotherapy is the first-line option for those patients. Traditional antitumor drugs have the disadvantages of poor biological distribution and pharmacokinetics, poor target selectivity, high resistance, and high toxicity to nontargeted tissues. Recently, the development of nanotechnology has significantly improved drug delivery to tumor sites by changing the physical and biological characteristics of drugs and nanocarriers to improve their pharmacokinetics and biological distribution and to selectively accumulate cytotoxic agents at tumor sites. Here, we systematically review the tumor microenvironment of HCC and the recent application of nanotechnology in HCC.

Investigations of nitazoxanide molecular targets and pathways for the treatment of hepatocellular carcinoma using network pharmacology and molecular docking

“…HCC often afflicts individuals with a history of hepatitis or cirrhosis. Owing to increasing malignancy and morbidity, it is the second leading cause of global cancer-related demise ( Khan and Lee, 2022 ; Yang et al, 2022 ). In the lack of viable HCC preventive or therapeutic interventions, emerging trends have shifted toward drug repurposing instead of conventional drug discovery and development due to the latter’s many constraints ( Pfab et al, 2021 ).…”

“…HCC is a kind of cancer that often affects people who have a history of hepatitis or cirrhosis. Owing to increasing malignancy and morbidity, it is the second leading cause of global cancer-related demise ( Khan and Lee, 2022 ; Yang et al, 2022 ). Several efficient therapeutic approaches, including biological therapy, interventional radiology, chemotherapy, resection, tumor ablation, transcatheter arterial chemical embolization (TACE), liver transplantation, etc., have been extensively employed in treating HCC in recent decades ( Stehlin et al, 1988 ; El-Serag, 2011 ; Balogh et al, 2016 ; Hilmi et al, 2020 ).…”

Intermittent Fasting Primes the Tumor Microenvironment and Improves Nanomedicine Delivery in Hepatocellular Carcinoma

“…[ 14 ] Delivery of conventional chemotherapeutics often exhibits unfavorable distribution, poor target selectivity and high toxicity to nontargeted tissues due to their systemic application and low specificity. [ 15 ] These issues can cause dose‐limiting side effects over time hindering their clinical application, and creating the need for refined treatment options. [ 16 ] Improving drug delivery can be achieved through nanomedicines, which uses physical and biological characteristics of nanocarriers to increase selective accumulation at tumor sites.…”

“…Organic nanoparticles like liposomes can help deliver drugs directly into cells, avoiding high concentrations of free drugs and reducing adverse reactions. [ 15 ] As the TME and tumor‐directed delivery of nanoparticles might be influenced by fasting, it could provide a useful strategy to further improve nanomedicine therapies.…”

Diagnostic accuracy and prognostic significance of Glypican-3 in hepatocellular carcinoma: A systematic review and meta-analysis

“…It has a strong potential to bind to functional biological macromolecules such as proteins and sugars, especially to a variety of cell growth factors, including vascular endothelial growth factor, epidermal growth factor, hepatocyte growth factor, fibroblast growth factor, and transforming growth factor-b. GPC-3 binds to a variety of growth factors to form receptor signal transduction complexes, which activate the tyrosine kinase activity of growth factor receptors, thereby regulating cell growth, differentiation, adhesion, proliferation, and migration, which may be related to the occurrence and progression of HCC (15)(16)(17)(18).…”