Tuesday, May 12, 2020

PLGA-thiol and Fol-PEG-COOH from PolyScitech used in nanoparticle cancer therapy



Cytochrome-c can be used to induce apoptosis (cell-death) in cancer cells. Recently, researchers at University of Puerto Rico, Universidad Central del Caribe, and Florida International University used PLGA-SH (AI025) and Folate-PEG-COOH (AE003) from PolySciTech (www.polyscitech.com) as part of their development of a cytochrome c delivery system for treatment of non-small cell lung cancer. Read more: Barcelo-Bovea, Vanessa, Irivette Dominguez-Martinez, Freisa Joaquin-Ovalle, Luis A. Amador, Elizabeth Castro-Rivera, Kristofer Medina-Alvarez, Anthony McGoron, Kai Griebenow, and Yancy Ferrer-Acosta. "Optimization and Characterization of Protein Nanoparticles for the Targeted and Smart Delivery of Cytochrome c to Non-Small Cell Lung Carcinoma." (2020). https://www.preprints.org/manuscript/202004.0221

“The delivery of Cytochrome c (Cyt c) to the cytosol stimulates apoptosis in cells were its release from mitochondria and apoptosis induction is inhibited. We developed a drug delivery system consisting of Cyt c nanoparticles decorated with folate-poly(ethylene glycol)-poly(lactic-co-glycolic acid)-thiol (FA-PEG-PLGA-SH) to deliver Cyt c into cancer cells and test their targeting in the Lewis Lung Carcinoma (LLC) mouse model. Cyt c-PLGA-PEG-FA nanoparticles (NPs) of 253 ± 55 and 354 ± 11 nm were obtained by Cyt c nanoprecipitation, followed by surface decoration with the co-polymer SH-PLGA-PEG-FA, and compared to a nanoparticle-free formulation. Overexpression of FA in LLC cells and internalization of Cyt c-PLGA-PEG-FA nanoparticles (NPs) was confirmed by confocal microscopy. Caspase activation assays show NPs retain 88-96% Cyt c activity. The NP formulations were more efficient in decreasing LLC cell viability than the NP-free formulation, with IC50: 49.2 to 70.1 μg/ml versus 129.5 μg/ml, respectively. Our NP system is thrice as selective towards cancerous than normal cells. In-vivo studies using tagged nanoparticles show accumulation in mouse LLC tumor 5 min post-injection. In conclusion, our NP delivery system for Cyt c shows superiority over the NP-free formulation and reaches a folic acid-overexpressing tumor in an immune-competent animal model.”

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