Preprint Article Version 1 This version is not peer-reviewed

Optimization and Characterization of Protein Nanoparticles for the Targeted and Smart Delivery of Cytochrome c to Non-Small Cell Lung Carcinoma

Version 1 : Received: 8 April 2020 / Approved: 14 April 2020 / Online: 14 April 2020 (14:27:15 CEST)

A peer-reviewed article of this Preprint also exists.

Barcelo-Bovea, V.; Dominguez-Martinez, I.; Joaquin-Ovalle, F.; Amador, L.A.; Castro-Rivera, E.; Medina-Álvarez, K.; McGoron, A.; Griebenow, K.; Ferrer-Acosta, Y. Optimization and Characterization of Protein Nanoparticles for the Targeted and Smart Delivery of Cytochrome c to Non-Small Cell Lung Carcinoma. Cancers 2020, 12, 1215. Barcelo-Bovea, V.; Dominguez-Martinez, I.; Joaquin-Ovalle, F.; Amador, L.A.; Castro-Rivera, E.; Medina-Álvarez, K.; McGoron, A.; Griebenow, K.; Ferrer-Acosta, Y. Optimization and Characterization of Protein Nanoparticles for the Targeted and Smart Delivery of Cytochrome c to Non-Small Cell Lung Carcinoma. Cancers 2020, 12, 1215.

Journal reference: Cancers 2020, 12, 1215
DOI: 10.3390/cancers12051215

Abstract

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.

Subject Areas

Cancer; cytochrome c; drug delivery; Lewis Lung Carcinoma; nanoprecipitation

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