How Integrin-Targeted Plaga-Chitosan Nanoparticles Are Used In Tumor Treatment
Since most chemotherapeutic drugs are toxic to normal cells, it is an important goal for cancer drug carrier development to achieve the appropriate concentration of therapeutic drugs at the location of cancer cells while reducing the exposure of normal cells to chemotherapeutic drugs. Chemotherapy is non-specific for normal cytotoxicity, mainly dose-dependent toxicity. Studies have found that targeted drug delivery systems show a higher affinity for tumor cells. Therefore, targeted nanoparticle-based drug delivery is a promising method to overcome this challenge.
In lung cancer clinical studies, overexpressing receptors on cancer cell surfaces are often used as targets for therapeutic and ligand / antibody-modified nanodrug delivery vehicles. Previous studies have shown that integrin (αvβ3) receptors are high expression receptors on tumor endothelium and tumor cell surfaces. Using arginine-glycine-aspartate (RGD) peptides to target the integrin (αvβ3) in tumor vascular endothelium to inhibit angiogenesis and metastasis is a common strategy targeting integrin receptors. Therefore, RGD sequences and integrins (αvβ3) are also used for targeted drug delivery and diagnostic in nanoparticles drug delivery systems. Integrin expression is relatively weak in normal cells. However, in some cells, such as lung fibroblasts, integrin is transiently overexpressed. Therefore, in the development of drug delivery based on integrin receptor-targeted nanoparticles, the impact of targeted drug delivery on normal cells that exhibit high levels of integrin receptor expression also needs to be considered. Through further research by researchers, a new integrin-targeted tumor therapy method has recently been discovered.
In this study, scientists designed the RGD-modified PLGA-chitosan-based nanoparticle system (PLGA-CSNP-RGD) for targeted non-small cell lung cancer (NSCLC) cells that highly express αv β3 integrin. The nanoparticle system has a drug-loaded PLGA core, and the surface is coated with chitosan, and a linear RGD peptide (GRGDSP) is combined with it. Since chitosan is a biocompatible cationic polymer, it has many functional groups for ligand modification. In addition, the chitosan coating enhances the stability of the particles and controls drug release. At the same time, the mucoadhesive properties of chitosan can satisfy the transmucosal delivery of drugs, especially through the intrapulmonary route. GRGDSP is a linear peptide that preferentially recognizes receptors expressed on the cell surface of intact αvβ3 and α5β1. In addition, GRGDSP peptides have several times the cell adhesion capacity of similar peptides that have an affinity for the fibronectin receptor. Therefore, these advantages of RGD peptides, chitosan and PLGA nanoparticles were used to develop new formulations targeted at integrin-targeted drug delivery in lung cancer cells.
In order to test the drug delivery effect of this PLGA-CSNP-RGD system on non-small cell lung cancer cells (overexpressing the integrin αvβ3 receptor), researchers used immunoblot analysis and flow cytometry to study the expression level of integrin αvβ3 in non-small cell lung cancer cells and normal cells. Targeted nanoparticles were then added to paclitaxel (PTX, an effective anticancer drug) and compared to cell killing efficiency with free PTX and non-targeted nanoparticles. The efficiency of PLGA-CSNP-RGD was then tested in normal cells of different NSCLC cell lines and different integrin expression levels. The results showed that the difference in toxicity between NSCLC and normal lung fibroblasts has been confirmed, while bronchial epithelial cells have less toxic response to PLGA-CSNP-RGD to PTX. Therefore, PLGA-CSNP-RGD is suitable as a delivery vehicle widely used for the treatment of lung cancer.