Artificial stem cells mediated inflammation-tropic delivery of antiviral drugs for pneumonia treatment

J Nanobiotechnology. 2022 Jul 16;20(1):335. doi: 10.1186/s12951-022-01547-x.

Abstract

Background: Cytomegalovirus (CMV) pneumonia is a major cause of morbidity and mortality in immunodeficiency individuals, including transplant recipients and Acquired Immune Deficiency Syndrome patients. Antiviral drugs ganciclovir (GCV) and phosphonoformate (PFA) are first-line agents for pneumonia caused by herpesvirus infection. However, the therapy suffers from various limitations such as low efficiency, drug resistance, toxicity, and lack of specificity.

Methods: The antiviral drugs GCV and PFA were loaded into the pH-responsive nanoparticles fabricated by poly(lactic-co-glycolic acid) (PLGA) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and further coated with cell membranes derived from bone marrow mesenchymal stem cells to form artificial stem cells, namely MPDGP. We evaluated the viral suppression effects of MPDGP in vitro and in vivo.

Results: MPDGP showed significant inflammation tropism and efficient suppression of viral replication and virus infection-associated inflammation in the CMV-induced pneumonia model. The synergistic effects of the combination of viral DNA elongation inhibitor GCV and viral DNA polymerase inhibitor PFA on suppressing the inflammation efficiently.

Conclusion: The present study develops a novel therapeutic intervention using artificial stem cells to deliver antiviral drugs at inflammatory sites, which shows great potential for the targeted treatment of pneumonia. To our best knowledge, we are the first to fabricate this kind of artificial stem cell to deliver antiviral drugs for pneumonia treatment.

Keywords: Antiviral drugs; Artificial stem cells; Cytomegalovirus; Inflammation-tropic delivery; Pneumonia.

MeSH terms

  • Antiviral Agents* / pharmacology
  • Antiviral Agents* / therapeutic use
  • Cytomegalovirus
  • Cytomegalovirus Infections / drug therapy
  • Fatty Acids, Monounsaturated / chemistry
  • Foscarnet / pharmacology
  • Foscarnet / therapeutic use
  • Ganciclovir / pharmacology
  • Ganciclovir / therapeutic use
  • Humans
  • Inflammation / drug therapy
  • Nanoparticle Drug Delivery System*
  • Pneumonia / drug therapy*
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Quaternary Ammonium Compounds / chemistry
  • Stem Cells

Substances

  • Antiviral Agents
  • Fatty Acids, Monounsaturated
  • Nanoparticle Drug Delivery System
  • Quaternary Ammonium Compounds
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Foscarnet
  • 1,2-dioleoyloxy-3-(trimethylammonium)propane
  • Ganciclovir