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

• Published in: Materials Science & Engineering C 2020-06, Vol.111, p.110760, Article 110760
• Main Authors: Meghani, Nileshkumar M., Amin, Hardik, Park, Chulhun, Cui, Jing-Hao, Cao, Qing-Ri, Choi, Kyung Hyun, Lee, Beom-Jin
• Format: Article
• Language: English
• Subjects: Active cancer targeting; Biocompatibility; Biocompatible Materials - chemistry; Biotechnology; Blood vessels; Breast cancer; Cancer; Cell Line, Tumor; Cell Survival - drug effects; Clathrin; Click Chemistry; Clickable fattigation nanoparticles; Docetaxel - chemistry; Docetaxel - metabolism; Docetaxel - pharmacology; Drug Carriers - chemistry; Drug delivery; Drug delivery systems; Drug Liberation; Dynamic flow; Gelatin; Gelatin - chemistry; Human serum albumin; Humans; Lung cancer; Lungs; Materials science; Microfluidics; Microscopy, Confocal; Mimicry; Morphology; Nanoparticles; Nanoparticles - chemistry; Particle Size; Particle size distribution; Protein corona; Protein Corona - chemistry; Protein interaction; Proteins; Serum albumin; Serum Albumin, Human - chemistry; Shear Strength; Shear stress; Size distribution; Tumor cell lines; Zeta potential
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2020.110760

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