Combinatory interpretation of protein corona and shear stress for active cancer targeting of bioorthogonally clickable gelatin-oleic nanoparticles.

Abstract

Nanoparticle-protein interactions under conditions mimicking physiology determine how nanoparticles (NPs) will behave inside blood vessels and, therefore, the overall outcome of the drug-delivery system. Here, for the first time, we explore the effects of bio-mimicking shear stress and protein corona conditions on novel active targeting of clickable fattigation nanoparticles (NPs) for cancer therapy. Active targeting dibenzocyclooctyne-functionalized biocompatible gelatin-oleic NPs (GON-DBCOs) via a bioorthogonal click reaction were prepared by the desolvation method for delivery of docetaxel (DTX) to lung and breast cancer models. The effect of shear stress (5 dyne/cm2) and human serum albumin (HSA) protein corona on the cellular behavior of NPs was explored under a dynamic microfluidic system in lung (A549) and breast (MCF-7) cancer cell lines. The developed drug-loaded NPs had a particle size of 300 nm, a narrow size distribution, positive zeta potential, high encapsulation efficacy (72.4%), and spherical morphology. The particle size of the protein corona-coated NPs increased to 341 nm with a negative zeta potential. The inhibitory dose (IC50) increased approximately 3- and 42-fold in A549 and MCF-7 cells, respectively, under dynamic microfluidic conditions compared to static conditions. Cellular uptake was significantly decreased in the presence of shear stress and a protein corona, compared with static conditions, in both lung (A549, **p < 0.01) and breast (MCF-7, *p < 0.05) cancer cell lines. Clathrin-and energy-dependent pathways were found to be involved in the cellular uptake of NPs. This study could serve as a vital tool for the evaluation of NPs under aggressive bio-mimicking conditions comprising shear stress and a protein corona to predict the in vivo performance of NPs and support the preclinical and clinical translation of NP drug delivery systems.

• Authors: Nileshkumar M Meghani, Hardik Amin, Chulhun Park, Jing-Hao Cui, Qing-Ri Cao, Kyung Hyun Choi, Beom-Jin Lee
• Journal: Materials science & engineering. C, Materials for biological applications (Mater Sci Eng C Mater Biol Appl) Vol. 111 Pg. 110760 (Jun 2020) ISSN: 1873-0191 [Electronic] Netherlands
• PMID: 32279783 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Biocompatible Materials
• Drug Carriers
• Protein Corona
• Docetaxel
• Gelatin
• Serum Albumin, Human

Topics

• Biocompatible Materials (chemistry)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Click Chemistry
• Docetaxel (chemistry, metabolism, pharmacology)
• Drug Carriers (chemistry)
• Drug Liberation
• Gelatin (chemistry)
• Humans
• Microscopy, Confocal
• Nanoparticles (chemistry)
• Particle Size
• Protein Corona (chemistry)
• Serum Albumin, Human (chemistry)
• Shear Strength