Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part I: In vitro Release and Intracellular Uptake Perspective
Autor: | Aliaa Nabil ElMeshad, Ulrike Breitinger, Iman Gomaa, Mahmoud H. Abdel-Kader, Hans-Georg Breitinger, Aya Ahmed Sebak, Mahmoud Hussien Farag |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
inorganic chemicals
active targeting Biophysics Intracellular Space Pharmaceutical Science Bioengineering Protein Corona Peptide 02 engineering and technology 010402 general chemistry 01 natural sciences intracellular uptake Peptides Cyclic Biomaterials chemistry.chemical_compound protein corona Polylactic Acid-Polyglycolic Acid Copolymer Drug Discovery mental disorders melanoma Humans Bradford protein assay health care economics and organizations Original Research chemistry.chemical_classification endogenous targeting Drug Carriers Chemistry Organic Chemistry technology industry and agriculture Biological Transport General Medicine respiratory system 021001 nanoscience & nanotechnology passive targeting Blood proteins In vitro 0104 chemical sciences PLGA Drug Liberation Nanoparticles Nanocarriers 0210 nano-technology Intracellular |
Zdroj: | International Journal of Nanomedicine |
ISSN: | 1178-2013 1176-9114 |
Popis: | Introduction Protein corona (PC) deposition on nanoparticles (NPs) in biological systems contributes to a great extent to NPs' fates; their targeting potential, the interaction with different biological systems and the subsequent functions. PC - when properly tuned - can serve as a potential avenue for optimization of NPs' use in cancer therapy. Methods Poly-lactic co-glycolic acid (PLGA)-based NPs exhibiting different physicochemical properties were fabricated and characterized. The PC makeup of these NPs were qualitatively and quantitatively analyzed by Western blot and Bradford assay, respectively. The effect of PC on the release of NPs' cargos and the intracellular uptake into B16F10 melanoma cells has been studied. Results The composition of NPs (polymeric PLGA NPs vs lipid-polymer hybrid NPs) and the conjugation of an active targeting ligand (cRGDyk peptide) represented the major determinants of the PC makeup of NPs. The in vitro release of the loaded cargos from the NPs depended on the PC and the presence of serum proteins in the release medium. Higher cumulative release has been recorded in the presence of proteins in the case of peptide conjugated NPs, cNPs, while the unconjugated formulations, uNPs, showed an opposite pattern. NPs intracellular uptake studies revealed important roles of distinct serum and cellular proteins on the extent of NPs' accumulation in melanoma cells. For example, the abundance of vitronectin (VN) protein from serum has been positively related to the intracellular accumulation of the NPs. Conclusion Careful engineering of nanocarriers can modulate the recruitment of some proteins suggesting a potential use for achieving endogenous targeting to overcome the current limitations of targeted delivery of chemotherapeutic agents. |
Databáze: | OpenAIRE |
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