Functional proteome of macrophage carried nanoformulated antiretroviral therapy demonstrates enhanced particle carrying capacity
| Autor: | Han Liu, Huangui Xiong, Andrea Martinez-Skinner, Howard E. Gendelman, Fang Yu, JoEllyn M McMillan, Ram S. Veerubhotla |
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| Rok vydání: | 2013 |
| Předmět: |
Drug
Cyclopropanes Chemokine Biodistribution Potassium Channels Proteome Anti-HIV Agents Pyridines media_common.quotation_subject Drug Compounding Atazanavir Sulfate Biochemistry Article Membrane Potentials Phagocytosis Cell Movement medicine Macrophage Humans Particle Size Cells Cultured media_common Drug Carriers Ritonavir biology Nanoart Macrophages General Chemistry Benzoxazines Cytoskeletal Proteins Alkynes Drug delivery Immunology biology.protein Nanoparticles Chemokines Drug carrier Oligopeptides medicine.drug |
| Zdroj: | Journal of proteome research. 12(5) |
| ISSN: | 1535-3907 |
| Popis: | Our laboratory has pioneered the development of long-acting nanoformulations of antiretroviral therapy (nanoART). NanoART serves to improve drug compliance, toxicities, and access to viral reservoirs. These all function to improve treatment of human immunodeficiency virus (HIV) infection. Formulations are designed to harness the carrying capacities of mononuclear phagocytes (MP; monocytes and macrophages) and to use these cells as Trojan horses for drug delivery. Such a drug distribution system limits ART metabolism and excretion while facilitating access to viral reservoirs. Our prior works demonstrated a high degree of nanoART sequestration in macrophage recycling endosomes with broad and sustained drug tissue biodistribution and depots with limited untoward systemic toxicities. Despite such benefits, the effects of particle carriage on the cells’ functional capacities remained poorly understood. Thus, we employed pulsed stable isotope labeling of amino acids in cell culture to elucidate the macrophage proteome and assess any alterations in cellular functions that would affect cell-drug carriage and release kinetics. NanoART-MP interactions resulted in the induction of a broad range of activation-related proteins that can enhance phagocytosis, secretory functions, and cell migration. Notably, we now demonstrate that particle-cell interactions serve to enhance drug loading while facilitating drug tissue depots and transportation. |
| Databáze: | OpenAIRE |
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