Single-Chain Polymer Nanoparticles Targeting the Ookinete Stage of Malaria Parasites

Naomi M. Hamelmann, Jan Willem D. Paats, Yunuen Avalos-Padilla, Elena Lantero, Lefteris Spanos, Inga Siden-Kiamos, Xavier Fernàndez-Busquets, Jos M.J. Paulusse*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)
70 Downloads (Pure)

Abstract

Malaria is an infectious disease transmitted by mosquitos, whose control is hampered by drug resistance evolution in the causing agent, protist parasites of the genus Plasmodium, as well as by the resistance of the mosquito to insecticides. New approaches to fight this disease are, therefore, needed. Research into targeted drug delivery is expanding as this strategy increases treatment efficacies. Alternatively, targeting the parasite in humans, here we use single-chain polymer nanoparticles (SCNPs) to target the parasite at the ookinete stage, which is one of the stages in the mosquito. This nanocarrier system provides uniquely sized and monodispersed particles of 5-20 nm, via thiol-Michael addition. The conjugation of succinic anhydride to the SCNP surface provides negative surface charges that have been shown to increase the targeting ability of SCNPs to Plasmodium berghei ookinetes. The biodistribution of SCNPs in mosquitos was studied, showing the presence of SCNPs in mosquito midguts. The presented results demonstrate the potential of anionic SCNPs for the targeting of malaria parasites in mosquitos and may lead to progress in the fight against malaria.

Original languageEnglish
Pages (from-to)56-64
Number of pages9
JournalACS Infectious Diseases
Volume9
Issue number1
DOIs
Publication statusPublished - 13 Jan 2023

Keywords

  • atovaquone
  • drug-conjugate
  • intramolecular crosslinking
  • Plasmodium berghei
  • single chain polymer nanoparticles
  • thiol-Michael addition
  • UT-Hybrid-D

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