Nano-Leish-IL: A novel iron oxide-based nanocomposite drug platform for effective treatment of cutaneous leishmaniasis

Sriram Kannan, Yifat Harel, Esthy Levy, Avishay Dolitzky, Assaf E. Sagiv, Saurav Aryal, Laila Suleman, Jean Paul Lellouche, Shulamit Michaeli

Research output: Contribution to journalArticlepeer-review

Abstract

Kinetoplastids are infamous parasites that include trypanosomes and Leishmania species. Here, we developed an anti-Leishmania nano-drug using ultra-small functional maghemite (γ-Fe2O3) nanoparticles (NPs) that were surface-doped by [CeLn]3/4+ to enable effective binding of the polycationic polyethylenebyimine (PEI) polymer by coordinative chemistry. This resulting nano-drug is cytolytic in-vitro to both Trypanosoma brucei parasites, the causative agent of sleeping sickness, as well as to three Leishmania species. The nano-drug induces the rupture of the single lysosome present in these parasites attributed to the PEI, leading to cytolysis. To evaluate the efficacy of a “cream-based” version of the nano-drug, which was termed “Nano-Leish-IL” for topical treatment of cutaneous leishmaniasis (CL), we developed a rapid screening method utilizing T. brucei parasites involved in social motility and demonstrated that functional NPs arrested the migration of the parasites. This assay presents a surrogate system to rapidly examine the efficacy of “cream-based” drugs in topical preparations against leishmaniasis, and possibly other dermal infectious diseases. The resulting Nano-Leish-IL topical preparation eliminated L. major infection in mice. Thus, this study presents a novel efficient nano-drug targeting the single lysosome of kinetoplastid parasites.

Original languageEnglish
Pages (from-to)203-215
Number of pages13
JournalJournal of Controlled Release
Volume335
DOIs
StatePublished - 10 Jul 2021
Externally publishedYes

Keywords

  • Cerium cation/complex doping
  • Iron oxide-based nanomaterials
  • Leishmania
  • Leishmaniasis
  • Nano-drug and drug delivery system
  • Parasites
  • Polyethyleneimine (PEI) polymers
  • Social motility
  • Trypanosoma brucei

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