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

Cancers

Anthony McGoron¹  Kai Griebenow²  LuisA. Amador²  Irivette Dominguez-Martinez²  Vanessa Barcelo-Bovea²  Freisa Joaquin-Ovalle²  Elizabeth Castro-Rivera³  Kristofer Medina-Álvarez³  Yancy Ferrer-Acosta³ 

[1] Department of Biomedical Engineering, Florida International University, FL 33174, USA;Department of Chemistry, University of Puerto Rico, San Juan 00925, Puerto Rico;Department of Neuroscience, Universidad Central del Caribe, Bayamon 00956, Puerto Rico;

关键词: cancer;    cytochrome c;    drug delivery;    Lewis Lung Carcinoma;    nanoprecipitation;    non-small cell lung carcinoma;   

DOI  :  10.3390/cancers12051215

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown