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Article

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

1
Department of Chemistry, University of Puerto Rico, San Juan 00925, Puerto Rico
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Molecular Sciences Research Center, San Juan 00926, Puerto Rico
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Department of Neuroscience, Universidad Central del Caribe, Bayamon 00956, Puerto Rico
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Department of Biomedical Engineering, Florida International University, Miami, FL 33174, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(5), 1215; https://doi.org/10.3390/cancers12051215
Received: 8 April 2020 / Revised: 7 May 2020 / Accepted: 11 May 2020 / Published: 13 May 2020
(This article belongs to the Section Methods and Technologies Development)
The delivery of Cytochrome c (Cyt c) to the cytosol stimulates apoptosis in cells where its release from mitochondria and apoptotic 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 tested 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. The internalization of Cyt c-PLGA-PEG-FA nanoparticles (NPs) in LLC cells was confirmed by confocal microscopy. NP caspase activation was more efficient than the NP-free formulation. Caspase activity assays showed NPs retained 88–96% Cyt c activity. The NP formulations were more effective in decreasing LLC cell viability than NP-free formulation, with IC50 49.2 to 70.1 μg/mL versus 129.5 μg/mL, respectively. Our NP system proved to be thrice as selective towards cancerous than normal cells. In vivo studies using near infrared-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. View Full-Text
Keywords: cancer; cytochrome c; drug delivery; Lewis Lung Carcinoma; nanoprecipitation; non-small cell lung carcinoma cancer; cytochrome c; drug delivery; Lewis Lung Carcinoma; nanoprecipitation; non-small cell lung carcinoma
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MDPI and ACS Style

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. https://doi.org/10.3390/cancers12051215

AMA Style

Barcelo-Bovea V, Dominguez-Martinez I, Joaquin-Ovalle F, Amador LA, 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(5):1215. https://doi.org/10.3390/cancers12051215

Chicago/Turabian Style

Barcelo-Bovea, Vanessa, Irivette Dominguez-Martinez, Freisa Joaquin-Ovalle, Luis A. Amador, Elizabeth Castro-Rivera, Kristofer Medina-Álvarez, Anthony McGoron, Kai Griebenow, and Yancy Ferrer-Acosta. 2020. "Optimization and Characterization of Protein Nanoparticles for the Targeted and Smart Delivery of Cytochrome c to Non-Small Cell Lung Carcinoma" Cancers 12, no. 5: 1215. https://doi.org/10.3390/cancers12051215

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