Functional proteome of macrophage carried nanoformulated antiretroviral therapy demonstrates enhanced particle carrying capacity

Andrea L. Martinez-Skinner, Ram S. Veerubhotla, Han Liu, Huangui Xiong, Fang Yu, Joellyn M. McMillan, Howard E. Gendelman

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Our laboratory developed long-acting nanoformulations of antiretroviral therapy (nanoART) to improve drug compliance, reduce toxicities, and facilitate access of drug to viral reservoirs. These all function to inevitably 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.

Original languageEnglish (US)
Pages (from-to)2282-2294
Number of pages13
JournalJournal of proteome research
Volume12
Issue number5
DOIs
StatePublished - May 3 2013

Keywords

  • cell function
  • monocyte-derived macrophages
  • nanoART
  • proteome
  • pulsed stable isotope labeling of amino acids in cell culture

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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