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Potent Virustatic Polymer-Lipid Nanomimics Block Viral Entry and Inhibit Malaria Parasites In Vivo.
Najer, Adrian; Blight, Joshua; Ducker, Catherine B; Gasbarri, Matteo; Brown, Jonathan C; Che, Junyi; Høgset, Håkon; Saunders, Catherine; Ojansivu, Miina; Lu, Zixuan; Lin, Yiyang; Yeow, Jonathan; Rifaie-Graham, Omar; Potter, Michael; Tonkin, Renée; Penders, Jelle; Doutch, James J; Georgiadou, Athina; Barriga, Hanna M G; Holme, Margaret N; Cunnington, Aubrey J; Bugeon, Laurence; Dallman, Margaret J; Barclay, Wendy S; Stellacci, Francesco; Baum, Jake; Stevens, Molly M.
  • Najer A; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, U.K.
  • Blight J; Department of Life Sciences, Imperial College London, London, SW7 2AZ, U.K.
  • Ducker CB; Department of Life Sciences, Imperial College London, London, SW7 2AZ, U.K.
  • Gasbarri M; Department of Life Sciences, Imperial College London, London, SW7 2AZ, U.K.
  • Brown JC; Institute of Materials, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
  • Che J; Department of Infectious Disease, Imperial College London, London, W2 1PG, U.K.
  • Høgset H; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, U.K.
  • Saunders C; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, U.K.
  • Ojansivu M; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, U.K.
  • Lu Z; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
  • Lin Y; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, U.K.
  • Yeow J; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, U.K.
  • Rifaie-Graham O; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, U.K.
  • Potter M; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, U.K.
  • Tonkin R; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, U.K.
  • Penders J; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, U.K.
  • Doutch JJ; Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, U.K.
  • Georgiadou A; Rutherford Appleton Laboratory, ISIS Neutron and Muon Source, STFC, Didcot OX11 ODE, U.K.
  • Barriga HMG; Department of Infectious Disease, Imperial College London, London, W2 1PG, U.K.
  • Holme MN; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
  • Cunnington AJ; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
  • Bugeon L; Department of Infectious Disease, Imperial College London, London, W2 1PG, U.K.
  • Dallman MJ; Department of Life Sciences, Imperial College London, London, SW7 2AZ, U.K.
  • Barclay WS; Department of Life Sciences, Imperial College London, London, SW7 2AZ, U.K.
  • Stellacci F; Department of Infectious Disease, Imperial College London, London, W2 1PG, U.K.
  • Baum J; Institute of Materials, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
  • Stevens MM; Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
ACS Cent Sci ; 8(9): 1238-1257, 2022 Sep 28.
Article in English | MEDLINE | ID: covidwho-1860279
ABSTRACT
Infectious diseases continue to pose a substantial burden on global populations, requiring innovative broad-spectrum prophylactic and treatment alternatives. Here, we have designed modular synthetic polymer nanoparticles that mimic functional components of host cell membranes, yielding multivalent nanomimics that act by directly binding to varied pathogens. Nanomimic blood circulation time was prolonged by reformulating polymer-lipid hybrids. Femtomolar concentrations of the polymer nanomimics were sufficient to inhibit herpes simplex virus type 2 (HSV-2) entry into epithelial cells, while higher doses were needed against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given their observed virustatic mode of action, the nanomimics were also tested with malaria parasite blood-stage merozoites, which lose their invasive capacity after a few minutes. Efficient inhibition of merozoite invasion of red blood cells was demonstrated both in vitro and in vivo using a preclinical rodent malaria model. We envision these nanomimics forming an adaptable platform for developing pathogen entry inhibitors and as immunomodulators, wherein nanomimic-inhibited pathogens can be secondarily targeted to sites of immune recognition.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: ACS Cent Sci Year: 2022 Document Type: Article Affiliation country: Acscentsci.1c01368

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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: ACS Cent Sci Year: 2022 Document Type: Article Affiliation country: Acscentsci.1c01368