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. Cancers2020, 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.
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. Cancers2020, 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.
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.
Keywords
Cancer; cytochrome c; drug delivery; Lewis Lung Carcinoma; nanoprecipitation
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
