| Autor: |
Olivieri PH Jr; Department of Biochemistry, Federal University of São Paulo, São Paulo, São Paulo 04044-020, Brazil., Assis IF; Department of Biochemistry, Federal University of São Paulo, São Paulo, São Paulo 04044-020, Brazil., Lima AF; Department of Biochemistry, Federal University of São Paulo, São Paulo, São Paulo 04044-020, Brazil., Hassan SA; Bioinformatics and Computational Biosciences Branch, OCICB, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, United States., Torquato RJS; Department of Biochemistry, Federal University of São Paulo, São Paulo, São Paulo 04044-020, Brazil., Hayashi JY; Department of Biochemistry, Federal University of São Paulo, São Paulo, São Paulo 04044-020, Brazil., Tashima AK; Department of Biochemistry, Federal University of São Paulo, São Paulo, São Paulo 04044-020, Brazil., Nader HB; Department of Biochemistry, Federal University of São Paulo, São Paulo, São Paulo 04044-020, Brazil., Salvati A; Department of Nanomedicine & Drug Targeting, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV Groningen, The Netherlands., Justo GZ; Department of Biochemistry, Federal University of São Paulo, São Paulo, São Paulo 04044-020, Brazil., Sousa AA; Department of Biochemistry, Federal University of São Paulo, São Paulo, São Paulo 04044-020, Brazil. |
| Abstrakt: |
Albumin-based nanoparticles (ABNPs) represent promising drug carriers in nanomedicine due to their versatility and biocompatibility, but optimizing their effectiveness in drug delivery requires understanding their interactions with and uptake by cells. Notably, albumin interacts with the cellular glycocalyx, a phenomenon particularly studied in endothelial cells. This observation suggests that the glycocalyx could modulate ABNP uptake and therapeutic efficacy, although this possibility remains unrecognized. In this study, we elucidate the critical role of the glycocalyx in the cellular uptake of a model ABNP system consisting of silica nanoparticles (NPs) coated with native, cationic, and anionic albumin variants (BSA, BSA+, and BSA-). Using various methodologies-including fluorescence anisotropy, dynamic light scattering, microscale thermophoresis, surface plasmon resonance spectroscopy, and computer simulations─we found that both BSA and BSA+, but not BSA-, interact with heparin, a model glycosaminoglycan (GAG). To explore the influence of albumin-GAG interactions on NP uptake, we performed comparative uptake studies in wild-type and GAG-mutated Chinese hamster ovary cells (CHO), along with complementary approaches such as enzymatic GAG cleavage in wild-type cells, chemical inhibition, and competition assays with exogenous heparin. We found that the glycocalyx enhances the cell uptake of NPs coated with BSA and BSA+, while serving as a barrier to the uptake of NPs coated with BSA-. Furthermore, we showed that harnessing albumin-GAG interactions increases cancer cell death induced by paclitaxel-loaded albumin-coated NPs. These findings underscore the importance of albumin-glycocalyx interactions in the rational design and optimization of albumin-based drug delivery systems. |
