مقالات پذیرفته شده در هفتمین کنگره بین المللی زیست پزشکی
The Importance of Nanomedicine in Hepatocellular Carcinoma
The Importance of Nanomedicine in Hepatocellular Carcinoma
Mohana Kamari,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Introduction: The most frequent type of primary liver cancer (HCC) is also the fifth most common cancer worldwide. It has a high mortality rate and kills more than 600,000 people per year. The majority of HCC patients are detected at advanced stages of the disease, when there are few and inefficient therapy choices available because of the insidious growing characteristic of the disease. Nanotechnology has emerged as a rapidly developing topic and a cutting-edge way to address the difficulties currently facing HCC therapy. Investigating Nanomedicine in Hepatocellular Carcinoma was the goal of this investigation.
Methods: This review study has written the from scientific databases such as Science Direct, Springer, Google Scholar, and PubMed.
Results: Recent research has highlighted the link between tumor cells and their surrounding microenvironment along with the fundamental role of the tumor microenvironment in hepatocarcinogenesis The tumor microenvironment is composed of; cells such as hepatic stellate cells, fibroblasts, immune cells, including regulatory and cytotoxic T cells and tumor-associated macrophages (TAMs), and endothelial cells, proteolytic enzymes including matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs), growth factors, for example, transforming growth factor b1 (TGF-β1) and platelet-derived growth factor (PDGF), inflammatory cytokines, and extracellular matrix (ECM). The EPR effect increases nanoparticle accumulation at the tumor site resulting in a more specific therapeutic targeting along with reduced toxicity of the therapeutic agents due to membrane hyperpermeability and absence of basement membrane in the tumor vasculature compared to normal tissue blood vessels pharmaceutics. Although the liver vasculature inherently possesses leaky vessels, the vasculature abnormalities in the presence of chronic liver diseases such as cirrhosis are ubiquitous Therefore, designing and developing different nano systems with particle size within the vasculature to selectively target HCC tumor cells would enable an effective drug delivery system in the setting of liver diseases. Another characteristic of the HCC tumor environment is the low extracellular pH, which lies between 6.0 and 7.0 as compared to normal tissues and blood with pH. This is due to the increased rate of glycolysis leading to the accumulation of lactic acid in hypoxic tumor cells. Changes in pH play a role in the delivery of therapeutic agents to the liver tumor cells: an acidic pH favors the cellular uptake of weakly acidic drugs and delays the uptake of weakly basic drugs. This consideration can also inform the synthesis of nanoparticles to provide optimal HCC tumor targeting.
Conclusion: The cutting-edge research and development in HCC nanomedicine have provided a powerful tool over traditional approaches for specific tumor targeting. Although designing a nano-drug delivery system is a complex process that requires optimization of its physicochemical properties, targeting HCC cells also requires a thorough understanding of the challenges such as a cirrhotic liver setting and the interaction between nanoparticles and the HCC tumor environment hindering its transition to clinical practice. There are several significant advantages of nanotechnology, ranging from effective targeting to reduced systemic toxicity. Currently, the only FDA-approved nanomedicine for various other cancer treatments includes; Doxil (liposomal doxorubicin), Onivyde (liposomal irinotecan), Abraxane (albumin-particle bound paclitaxel), Eligard (leuprolide acetate), and Vyxeos (liposomal cytarabine and daunorubicin) with none specific to HCC. Interestingly, the most crucial part of designing HCC nanomedicine requires formulating nano systems with ligands specific to the receptors discussed above, such as ASGPR, GPC3, TfR, FR, and SR-B1. Nano systems with such targeting ligands have proven their efficacy for anti-cancer treatment in several in vitro and in vivo studies. Therefore, there has been progressive development in specific targeted nano delivery systems for HCC, and there is excellent potential for translation of this strategy into the clinical context.