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.
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http://dx.doi.org/10.2147/IJN.S273713 | DOI Listing |
Bioorg Chem
December 2024
Universidade da Coruña, CICA - Centro Interdisciplinar de Química e Bioloxía and Departamento de Química, Facultad de Ciencias, Campus A Zapateira, 15071 A Coruña, Spain. Electronic address:
In this study, a series of BODIPY dyes were synthesized, containing various substituents at meso position. Further functionalization of the BODIPY framework at C2 and C2-C6 position(s) by palladium-catalysed cross-coupling reactions using organoindium reagents (RIn) was efficiently assessed, starting from C2(6)-halogenated BODIPYs, and their optical properties were measured. The cytotoxicity of BODIPY dyes on SH-SY5Y neuronal cells by MTT assay showed that those compounds bearing thien-2-yl and benzonitrile moieties at meso position, exhibited great efficiency in maintaining cell viability under all tested conditions (up to 50 µM for 24 h and 48 h).
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Laboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte-UFRN, Natal, RN, Brazil. Electronic address:
Chagas disease is a neglected tropical disease caused by the protozoan Trypanosoma cruzi, remains a significant global health challenge. Currently, benznidazole (BNZ) is the primary treatment in many countries. However, this drug is limited by low bioavailability, significant host toxicity, and reduced efficacy in chronic disease phase.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Background: While disease-modifying treatments that reduce Aβ have been recently approved by the FDA, the identification of novel therapeutic targets and strategies that target underlying mechanisms to delay the AD development are still needed. Abnormal brain energy homeostasis and mitochondria dysfunction are observed early in AD. Therefore, the development of treatments to restore these defects could be beneficial.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of California, Irvine, Irvine, CA, USA.
Background: The complement system contributes to enhanced inflammation and cognitive decline in Alzheimer's disease (AD). Previous studies have demonstrated constitutive deletion of the classical initiator protein, C1q, reduces glial activity and attenuates neuronal loss in AD mouse models. As it is now known that microglia are the primary producers of C1q in the brain, the objective of this study was to determine if microglial specific deletion of C1q would reduce lysosome associated phagocytosis of Vglut1, an excitatory synapse marker, and if reductions in the phagocytosis of Vglut1 would be accompanied by a reduction in the phagocytosis of beta-amyloid.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder marked by progressive memory loss and cognitive decline. The precise molecular mechanisms underlying AD pathogenesis remain uncertain, underscoring the need for further investigation to identify novel therapeutic targets. We recently demonstrated that mitochondrial calcium (Ca) overload significantly contributes to the development of AD, capable of independently driving AD-like pathology.
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