The cellular affinity of micro-/nanoparticles is the precondition for cellular recognition, cellular uptake, and activation, which are essential for drug delivery and immune response. The present study stemmed from the observation that the effects of charge, size, and shape of solid particles on cell affinity are usually considered, but we seldom realize the essential role of softness, dynamic restructuring phenomenon, and complex interface interaction in cellular affinity. Here, we developed poly-lactic-co-glycolic acid (PLGA) nanoparticle-stabilized Pickering emulsion (PNPE) that overcame the shortcomings of rigid forms and simulated the flexibility and fluidity of pathogens. A method was set up to test the affinity of PNPE to cell surfaces and elaborate on the subsequent internalization by immune cells. The affinity of PNPE to bio-mimetic extracellular vesicles (bEVs)-the replacement for bone marrow dendritic cells (BMDCs)-was determined using a quartz crystal microbalance with dissipation monitoring (QCM-D), which allowed real-time monitoring of cell-emulsion adhesion. Subsequently, the PNPE was used to deliver the antigen (ovalbumin, OVA) and the uptake of the antigens by BMDCs was observed using confocal laser scanning microscope (CLSM). Representative results showed that the PNPE immediately decreased frequency (ΔF) when it encountered the bEVs, indicating rapid adhesion and high affinity of the PNPE to the BMDCs. PNPE showed significantly stronger binding to the cell membrane than PLGA microparticles (PMPs) and AddaVax adjuvant (denoted as surfactant-stabilized nano-emulsion [SSE]). Furthermore, owing to the enhanced cellular affinity to the immunocytes through dynamic curvature changes and lateral diffusions, antigen uptake was subsequently boosted compared with PMPs and SSE. This protocol provides insights for designing novel formulations with high cell affinity and efficient antigen internalization, providing a platform for the development of efficient vaccines.
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http://dx.doi.org/10.3791/64406 | DOI Listing |
BMC Chem
January 2025
Energy Systems Engineering Department, Engineering Faculty, Adana Alparslan Türkeş Science and Technology University, 01250, Adana, Türkiye.
Although the antiallergic properties of compounds such as CAPE, Melatonin, Curcumin, and Vitamin C have been poorly discussed by experimental studies, the antiallergic properties of these famous molecules have never been discussed with calculations. The histamine-1 receptor (H1R) belongs to the family of rhodopsin-like G-protein-coupled receptors expressed in cells that mediate allergies and other pathophysiological diseases. In this study, pharmacological activities of FDA-approved second generation H1 antihistamines (Levocetirizine, desloratadine and fexofenadine) and molecules such as CAPE, Melatonin, Curcumin, Vitamin C, ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) profiles, density functional theory (DFT), molecular docking, biological targets and activities were compared by calculating.
View Article and Find Full Text PDFJ Infect
January 2025
Center for Cellular and Molecular Diagnostics, Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, USA. Electronic address:
Objectives: Pediatric tuberculosis (TB) diagnosis is complicated by challenges in obtaining invasive respiratory specimens that frequently contain few Mycobacterium tuberculosis (Mtb) bacilli. We report the diagnostic performance of an Mtb antigen-derived peptide (MAP-TB) assay and its ability to monitor TB treatment response.
Methods: Study cohorts enrolled children who presented with presumptive TB at two hospitals in South Africa from 2012 to 2017 (157 children aged <13 years) and at community-based clinics in the Dominican Republic from 2019 to 2023 (101 children aged <18 years).
Eur J Pharmacol
January 2025
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan province, P.R. China. Electronic address:
FOXM1 is the "Achilles' heel" of cancers and hence the potential therapeutic target for anticancer drug discovery. In this work, we selected high affinity peptides against the protein of human DNA binding domain of FOXM1 (FOXM1-DBD) from the disulfide-constrained, phage displayed random cyclic heptapeptide library Ph.D.
View Article and Find Full Text PDFImmunity
December 2024
Division of Oncogenomics, Oncode institute, the Netherlands Cancer Institute, Amsterdam, the Netherlands; Erasmus MC, Department of Genetics, Rotterdam University, Rotterdam, the Netherlands. Electronic address:
Prolonged exposure to interferon-gamma (IFNγ) and the associated increased expression of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) create an intracellular shortage of tryptophan in the cancer cells, which stimulates ribosomal frameshifting and tryptophan to phenylalanine (W>F) codon reassignments during protein synthesis. Here, we investigated whether such neoepitopes can be useful targets of adoptive T cell therapy. Immunopeptidomic analyses uncovered hundreds of W>F neoepitopes mainly presented by the HLA-A24:02 allele.
View Article and Find Full Text PDFCurr Pharm Des
January 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri 38039, Turkey.
Background: Psychosis, marked by detachment from reality, includes symptoms like hallucinations and delusions. Traditional herbal remedies like kratom are gaining attention for psychiatric conditions. This was aimed at comprehending the molecular mechanisms of Kratom's antipsychotic effects utilizing a multi-modal computational approach.
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