Chemodrug delivery using integrin-targeted PLGA-Chitosan nanoparticle for lung cancer therapy

Abstract

In this study, we report the efficacy of RGD (arginine-glycine-aspartic acid) peptide-modified polylactic acid-co-glycolic acid (PLGA)-Chitosan nanoparticle (CSNP) for integrin αvβ3 receptor targeted paclitaxel (PTX) delivery in lung cancer cells and its impact on normal cells. RGD peptide-modified chitosan was synthesized and then coated onto PTX-PLGA nanoparticles prepared by emulsion-solvent evaporation. PTX-PLGA-CSNP-RGD displayed favorable physicochemical properties for a targeted drug delivery system. The PTX-PLGA-CSNP-RGD system showed increased uptake via integrin receptor mediated endocytosis, triggered enhanced apoptosis, and induced G2/M cell cycle arrest and more overall cytotoxicity than its non-targeted counterpart in cancer cells. PTX-PLGA-CSNP-RGD showed less toxicity in lung fibroblasts than in cancer cells, may be attributed to low drug sensitivity, nevertheless the study invited close attention to their transient overexpression of integrin αvβ3 and cautioned against corresponding uptake of toxic drugs, if any at all. Whereas, normal human bronchial epithelial (NHBE) cells with poor integrin αvβ3 expression showed negligible toxicity to PTX-PLGA-CSNP-RGD, at equivalent drug concentrations used in cancer cells. Further, the nanoparticle demonstrated its capacity in targeted delivery of Cisplatin (CDDP), a drug having physicochemical properties different to PTX. Taken together, our study demonstrates that PLGA-CSNP-RGD is a promising nanoplatform for integrin targeted chemotherapeutic delivery to lung cancer.

Tetrac-decorated chitosan-coated PLGA nanoparticles as a new platform for targeted delivery of SN38

“…Previously, it was shown that the chitosan coating is a successful approach for preparation of sustained release system of various cargos, increase cellular uptake of PLGA-based NPs and finally enhance therapeutic index [9,10].…”

“…Tetrac (tetraiodothyroacetic acid) is a deaminated thyroid hormone analogue which specifically binds to Avb3 integrin overexpressed on tumour endothelial cells and inhibits the binding of its agonists which are thyroid hormones [10]. It was demonstrated that L-thyroxine (T4) induces the proliferation of cancer cells by activation of MAPK (ERK1,2) signalling pathway.…”

Targeting Integrins in Cancer Nanomedicine: Applications in Cancer Diagnosis and Therapy

“…In fact, several studies on the use of ligand-mediated "smart drug delivery systems" have revealed that therapeutic agents can be more specifically transported to tumor sites by targeting αvβ3-integrins on cancer cells, and these types of agents have proven to be efficient in a cancer therapy regime [148][149][150][151]. Several typical chemotherapeutic agents, such as doxorubicin [145,[152][153][154], cisplatin [149], and paclitaxel [155][156][157], have been combined with RGD-conjugated NPs to target integrin-overexpressing tumors.…”

Hypothesis: Advanced Biotechnological Treatment Approaches Against SARS-CoV-2 (COVID-19)

“…Chitosan's has muco-adhesive property. Therefore, it can be exploited for trans-mucosal delivery of drugs, especially through the intrapulmonary way (15). We also added chitosan polymer to our project because it is suitable for ligand modification, has mucoadhesive properties and increases the particle stability.…”