{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T14:48:33Z","timestamp":1774450113208,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Science, Innovation and Universities (http:\/\/www.ciencia.gob.es\/)","award":["PCIN-2017-100"],"award-info":[{"award-number":["PCIN-2017-100"]}]},{"name":"Spanish Ministry of Science, Innovation and Universities (http:\/\/www.ciencia.gob.es\/)","award":["RTI2018-094579-B-I00"],"award-info":[{"award-number":["RTI2018-094579-B-I00"]}]},{"name":"ERA-NET Cofund EURONANOMED (http:\/\/euronanomed.net\/)","award":["2017-178 (NANOpheles)"],"award-info":[{"award-number":["2017-178 (NANOpheles)"]}]},{"name":"Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (https:\/\/ghtm.ihmt.unl.pt\/)","award":["UID\/Multi\/04413\/2013"],"award-info":[{"award-number":["UID\/Multi\/04413\/2013"]}]},{"name":"BIOIBERICA","award":["Research Agreement"],"award-info":[{"award-number":["Research Agreement"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Innovative antimalarial strategies are urgently needed given the alarming evolution of resistance to every single drug developed against Plasmodium parasites. The sulfated glycosaminoglycan heparin has been delivered in membrane feeding assays together with Plasmodium berghei-infected blood to Anopheles stephensi mosquitoes. The transition between ookinete and oocyst pathogen stages in the mosquito has been studied in vivo through oocyst counting in dissected insect midguts, whereas ookinete interactions with heparin have been followed ex vivo by flow cytometry. Heparin interferes with the parasite\u2019s ookinete\u2013oocyst transition by binding ookinetes, but it does not affect fertilization. Hypersulfated heparin is a more efficient blocker of ookinete development than native heparin, significantly reducing the number of oocysts per midgut when offered to mosquitoes at 5 \u00b5g\/mL in membrane feeding assays. Direct delivery of heparin to mosquitoes might represent a new antimalarial strategy of rapid implementation, since it would not require clinical trials for its immediate deployment.<\/jats:p>","DOI":"10.3390\/biom10081136","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T06:16:47Z","timestamp":1596435407000},"page":"1136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Heparin Administered to Anopheles in Membrane Feeding Assays Blocks Plasmodium Development in the Mosquito"],"prefix":"10.3390","volume":"10","author":[{"given":"Elena","family":"Lantero","sequence":"first","affiliation":[{"name":"Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10\u201312, ES-08028 Barcelona, Spain"},{"name":"Barcelona Institute for Global Health (ISGlobal, Hospital Cl\u00ednic-Universitat de Barcelona), Rossell\u00f3 149-153, ES-08036 Barcelona, Spain"}]},{"given":"Jessica","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT-NOVA), Rua da Junqueira 100, 1349-008 Lisbon, Portugal"}]},{"given":"Carlos Ra\u00fal","family":"Al\u00e1ez-Vers\u00f3n","sequence":"additional","affiliation":[{"name":"BIOIBERICA S.A.U., Pol\u00edgon Industrial \u201cMas Puigvert\u201d, Ctra. N-II, km. 680.6, ES-08389 Palafolls, Spain"}]},{"given":"Joana","family":"Gomes","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT-NOVA), Rua da Junqueira 100, 1349-008 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7939-772X","authenticated-orcid":false,"given":"Henrique","family":"Silveira","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT-NOVA), Rua da Junqueira 100, 1349-008 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0313-0778","authenticated-orcid":false,"given":"Fatima","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT-NOVA), Rua da Junqueira 100, 1349-008 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4622-9631","authenticated-orcid":false,"given":"Xavier","family":"Fern\u00e0ndez-Busquets","sequence":"additional","affiliation":[{"name":"Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10\u201312, ES-08028 Barcelona, Spain"},{"name":"Barcelona Institute for Global Health (ISGlobal, Hospital Cl\u00ednic-Universitat de Barcelona), Rossell\u00f3 149-153, ES-08036 Barcelona, Spain"},{"name":"Nanoscience and Nanotechnology Institute (IN2UB, Universitat de Barcelona), Mart\u00ed i Franqu\u00e8s 1, ES-08028 Barcelona, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,1]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2019). World Malaria Report 2019, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1475-2875-11-70","article-title":"The biology of sexual development of Plasmodium: The design and implementation of transmission-blocking strategies","volume":"11","author":"Sinden","year":"2012","journal-title":"Malar. J."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Delves, M., Plouffe, D., Scheurer, C., Meister, S., Wittlin, S., Winzeler, E., Sinden, R.E., and Leroy, D. (2012). The activities of current antimalarial drugs on the life cycle stages of Plasmodium: A comparative study with human and rodent parasites. PLoS Med., 9.","DOI":"10.1371\/journal.pmed.1001169"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11193","DOI":"10.1038\/srep11193","article-title":"Comparative assessment of transmission-blocking vaccine candidates against Plasmodium falciparum","volume":"5","author":"Kapulu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1128\/iai.65.3.1109-1113.1997","article-title":"A novel malaria protein, Pfs28, and Pfs25 are genetically linked and synergistic as falciparum malaria transmission-blocking vaccines","volume":"65","author":"Duffy","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.exppara.2010.08.015","article-title":"The role of Pvs28 in sporozoite development in Anopheles sinensis and its longevity in BALB\/c mice","volume":"127","author":"Kim","year":"2011","journal-title":"Exp. Parasitol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21824","DOI":"10.1074\/jbc.M401979200","article-title":"A binding site for highly sulfated heparan sulfate is identified in the N terminus of the circumsporozoite protein: Significance for malarial sporozoite attachment to hepatocytes","volume":"279","author":"Ancsin","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4559","DOI":"10.1182\/blood-2009-09-243725","article-title":"Interactions with heparin-like molecules during erythrocyte invasion by Plasmodium falciparum merozoites","volume":"115","author":"Boyle","year":"2010","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mathias, D.K., Pastrana-Mena, R., Ranucci, E., Tao, D., Ferruti, P., Ortega, C., Staples, G.O., Zaia, J., Takashima, E., and Tsuboi, T. (2013). A small molecule glycosaminoglycan mimetic blocks Plasmodium invasion of the mosquito midgut. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003757"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15882","DOI":"10.1073\/pnas.0706340104","article-title":"Plasmodium falciparum ookinetes require mosquito midgut chondroitin sulfate proteoglycans for cell invasion","volume":"104","author":"Dinglasan","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.nano.2016.09.010","article-title":"Adaptation of targeted nanocarriers to changing requirements in antimalarial drug delivery","volume":"13","author":"Marques","year":"2017","journal-title":"Nanomed. NBM"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"26635","DOI":"10.1074\/jbc.M401385200","article-title":"Plasmodium ookinete-secreted proteins secreted through a common micronemal pathway are targets of blocking malaria transmission","volume":"279","author":"Li","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0008-6215(97)10060-X","article-title":"Conformational changes and anticoagulant activity of chondroitin sulfate following its O-sulfonation","volume":"306","author":"Maruyama","year":"1998","journal-title":"Carbohydr. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.molbiopara.2004.04.007","article-title":"A Plasmodium berghei reference line that constitutively expresses GFP at a high level throughout the complete life cycle","volume":"137","author":"Trueman","year":"2004","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1111\/j.1462-5822.2004.00394.x","article-title":"Real-time, in vivo analysis of malaria ookinete locomotion and mosquito midgut invasion","volume":"6","author":"Vlachou","year":"2004","journal-title":"Cell. Microbiol."},{"key":"ref_16","unstructured":"M\u00e9nard, R. (2013). Assessing transmission blockade in Plasmodium spp.. Malaria: Methods and Protocols, Humana Press."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bansal, A., Molina-Cruz, A., Brzostowski, J., Mu, J., and Miller, L.H. (2017). Plasmodium falciparum calcium-dependent protein kinase 2 is critical for male gametocyte exflagellation but not essential for asexual proliferation. mBio, 8.","DOI":"10.1128\/mBio.01656-17"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"391S","DOI":"10.1042\/bst019391s","article-title":"Ca2+-heparin interaction investigated polarimetrically","volume":"19","author":"Grant","year":"1991","journal-title":"Biochem. Soc. Trans."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"242","DOI":"10.4269\/ajtmh.2007.77.242","article-title":"Effects of anticoagulants on Plasmodium vivax oocyst development in Anopheles albimanus mosquitoes","volume":"77","author":"Solarte","year":"2007","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"976827","DOI":"10.1155\/2010\/976827","article-title":"The coming-out of malaria gametocytes","volume":"2010","author":"Kuehn","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6221","DOI":"10.1093\/emboj\/18.22.6221","article-title":"CTRP is essential for mosquito infection by malaria ookinetes","volume":"18","author":"Dessens","year":"1999","journal-title":"EMBO J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/nrd4573","article-title":"Malaria medicines: A glass half full?","volume":"14","author":"Wells","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"579","DOI":"10.2217\/fmb.14.30","article-title":"Antimalarial drug delivery to the mosquito: An option worth exploring?","volume":"9","author":"Paaijmans","year":"2014","journal-title":"Future Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/1475-2875-12-153","article-title":"Ivermectin to reduce malaria transmission: A research agenda for a promising new tool for elimination","volume":"12","author":"Chaccour","year":"2013","journal-title":"Malar. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/j.1365-2915.2005.00565.x","article-title":"Optimal life stage for radiation sterilization of Anopheles males and their fitness for release","volume":"19","author":"Andreasen","year":"2005","journal-title":"Med. Vet. Entomol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41586-019-0973-1","article-title":"Exposing Anopheles mosquitoes to antimalarials blocks Plasmodium parasite transmission","volume":"567","author":"Paton","year":"2019","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.ibmb.2009.09.007","article-title":"Ingested double-stranded RNAs can act as species-specific insecticides","volume":"39","author":"Whyard","year":"2009","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/j.1365-2583.2010.01029.x","article-title":"Chitosan\/double-stranded RNA nanoparticle-mediated RNA interference to silence chitin synthase genes through larval feeding in the African malaria mosquito (Anopheles gambiae)","volume":"19","author":"Zhang","year":"2010","journal-title":"Insect Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1161\/01.CIR.23.4.578","article-title":"Plasma heparin levels in normal man","volume":"23","author":"Engelberg","year":"1961","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e00709","DOI":"10.1128\/AAC.00709-17","article-title":"Identification of heparin modifications and polysaccharide inhibitors of Plasmodium falciparum merozoite invasion that have potential for novel drug development","volume":"61","author":"Boyle","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1080\/10739680701451516","article-title":"Blood coagulation, inflammation, and malaria","volume":"15","author":"Francischetti","year":"2008","journal-title":"Microcirculation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1590\/s1678-9946201860045","article-title":"Artificial blood feeding for Culicidae colony maintenance in laboratories: Does the blood source condition matter?","volume":"60","author":"Dias","year":"2018","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2174\/1871525717666190617120045","article-title":"Artificial blood: A futuristic dimension of modern day transfusion sciences","volume":"17","author":"Haldar","year":"2019","journal-title":"Cardiovasc. Hematol. Agents Med. Chem."},{"key":"ref_34","first-page":"e60144","article-title":"A blood-free diet to rear anopheline mosquitoes","volume":"155","author":"Marques","year":"2020","journal-title":"J. Vis. Exp."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17807","DOI":"10.1038\/s41598-018-35886-3","article-title":"Fresh-blood-free diet for rearing malaria mosquito vectors","volume":"8","author":"Marques","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gonzales, K.K., and Hansen, I.A. (2016). Artificial diets for mosquitoes. Int. J. Environ. Res. Public Health, 13.","DOI":"10.3390\/ijerph13121267"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.actatropica.2018.04.009","article-title":"Artificial blood feeders for mosquito and ticks-Where from, where to?","volume":"183","author":"Romano","year":"2018","journal-title":"Acta Trop."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/8\/1136\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:53:35Z","timestamp":1760176415000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/8\/1136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,1]]},"references-count":37,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["biom10081136"],"URL":"https:\/\/doi.org\/10.3390\/biom10081136","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,1]]}}}