PAMAM dendrimers form strong protein conjugates that are used in drug delivery systems. We report the thermodynamic and binding analysis of polyamidoamine (PAMAM-G4) conjugation with human serum albumin (HSA), bovine serum albumin (BSA) and milk beta-lactoglobulin (b-LG) in aqueous solution at physiological pH. Hydrophobicity played a major role in PAMAM-protein interactions with more hydrophobic b-LG forming stronger polymer-protein conjugates. Thermodynamic parameters showed PAMAM-protein bindings occur via hydrophobic and H-bonding contacts for b-LG, while van der waals and H-bonding interactions prevail in HSA and BSA-polymer conjugates. The protein loading efficacy was 45-55%. PAMAM complexation induced major alterations of protein conformation. TEM images show major polymer morphological changes upon protein conjugation.
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http://dx.doi.org/10.1016/j.colsurfb.2016.11.037 | DOI Listing |
BMC Pharmacol Toxicol
January 2025
Biochemistry Department, Faculty of Science, Tanta University, Tanta, Egypt.
Background: Naringenin, a flavonoid compound found in citrus fruits, possesses valuable anticancer properties. However, its potential application in cancer treatment is limited by poor bioavailability and pharmacokinetics at tumor sites. To address this, Naringenin nanoparticles (NARNPs) were prepared using the emulsion diffusion technique and their anticancer effects were investigated in HepG2 cells.
View Article and Find Full Text PDFDrug Deliv Transl Res
January 2025
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, FI-00014, Finland.
Functionalization of polymer nanoparticles (NPs) with targeting peptides is of interest for drug delivery applications to enhance tumor accumulation and penetration. Herein, we evaluated the feasibility of two different methods for the attachment of a tumor-penetrating peptide LinTT1 (AKRGARSTA) to poly(ethylene glycol)-block-poly(ε-caprolactone) (PCL-PEG) NPs: (1) "post-conjugation" onto pre-formed nanoparticles, and (2) "pre-conjugation", the synthesis and purification of peptide-polymer conjugates and subsequent nanoprecipitation of the conjugates diluted with non-functionalized polymers. Conjugation of the labelled peptide via maleimide-thiol chemistry was verified by gel permeation chromatography (GPC) and fluorescence measurements.
View Article and Find Full Text PDFCancer Immunol Immunother
January 2025
Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, NIH, 10 Center Drive, Bethesda, MD, 20892, USA.
Tissue factor (TF) is a cell surface protein that plays a role in blood clotting but is also commonly expressed in many cancers. Recent research implicated TF in cancer proliferation, metastasis, angiogenesis, and immune escape. Therefore, TF can be considered a viable therapeutic target against cancer.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
New York University Grossman School of Medicine, New York, NY, USA.
Background: Synucleinopathies lack cures. Antibody therapies targeting α-synuclein aim to inhibit aggregation and enhance degradation, but have limited brain entry because of size (150kDa). Smaller single-domain antibodies (sdAbs, 15kDa) have substantially improved brain uptake.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most prevalent form of late-life dementia. The ε2 allele of the APOE gene encoding apolipoprotein E (APOE2) is associated with lower susceptibility to AD among the three genotypes (ε2, ε3, ε4), while APOE4 is the strongest genetic risk factor for late-onset AD. APOE plays a critical role in maintaining synaptic plasticity and neuronal function by controlling lipid homeostasis, with APOE2 having a superior function.
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