TY - JOUR
T1 - Single-Chain Polymer Nanoparticles Targeting the Ookinete Stage of Malaria Parasites
AU - Hamelmann, Naomi M.
AU - Paats, Jan Willem D.
AU - Avalos-Padilla, Yunuen
AU - Lantero, Elena
AU - Spanos, Lefteris
AU - Siden-Kiamos, Inga
AU - Fernàndez-Busquets, Xavier
AU - Paulusse, Jos M.J.
N1 - Funding Information:
This research was funded through the EuroNanoMed III research program (Ref. EURO-NANOMED2017-178), as well as by Alzheimer Netherlands and co-funded by the PPP Allowance made available by Health─Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. This work was supported by grant PCIN-2017-100, funded by Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación, which included FEDER funds. ISGlobal and IBEC are members of the CERCA Programme, Generalitat de Catalunya. We acknowledge support from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S). This research is part of ISGlobal’s Program on the Molecular Mechanisms of Malaria, which is partially supported by the Fundación Ramón Areces.
Publisher Copyright:
© 2022 The Authors. Published by American Chemical Society.
PY - 2023/1/13
Y1 - 2023/1/13
N2 - 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.
AB - 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.
KW - atovaquone
KW - drug-conjugate
KW - intramolecular crosslinking
KW - Plasmodium berghei
KW - single chain polymer nanoparticles
KW - thiol-Michael addition
KW - UT-Hybrid-D
UR - https://www.scopus.com/pages/publications/85144271460
U2 - 10.1021/acsinfecdis.2c00336
DO - 10.1021/acsinfecdis.2c00336
M3 - Article
C2 - 36516858
AN - SCOPUS:85144271460
SN - 2373-8227
VL - 9
SP - 56
EP - 64
JO - ACS Infectious Diseases
JF - ACS Infectious Diseases
IS - 1
ER -
SDG 3 Good Health and Well-being