Potent Virustatic Polymer-Lipid Nanomimics Block Viral Entry and Inhibit Malaria Parasites In Vivo

被引：8

作者：

Najer, Adrian ^{[1
,4
,5
,6
]}

Blight, Joshua ^{[1
]}

Ducker, Catherine B. ^{[1
]}

Gasbarri, Matteo ^{[2
]}

Brown, Jonathan C. ^{[3
]}

Che, Junyi ^{[4
,5
,6
]}

Hogset, Hakon ^{[4
,5
,6
]}

Saunders, Catherine ^{[4
,5
,6
]}

Ojansivu, Miina ^{[7
]}

Lu, Zixuan ^{[4
,5
,6
]}

Lin, Yiyang ^{[4
,5
,6
]}

Yeow, Jonathan ^{[4
,5
,6
]}

Rifaie-Graham, Omar ^{[4
,5
,6
]}

Potter, Michael ^{[4
,5
,6
]}

Tonkin, Renee ^{[4
,5
,6
]}

Penders, Jelle ^{[4
,5
,6
]}

Doutch, James J. ^{[8
]}

Georgiadou, Athina ^{[3
]}

Barriga, Hanna M. G. ^{[7
]}

Holme, Margaret N. ^{[7
]}

Cunnington, Aubrey J. ^{[3
]}

Bugeon, Laurence ^{[1
]}

Dallman, Margaret J. ^{[1
]}

Barclay, Wendy S. ^{[3
]}

Stellacci, Francesco ^{[2
,9
]}

Baum, Jake ^{[1
,10
]}

Stevens, Molly M. ^{[4
,5
,6
,7
]}

机构：

[1] Imperial Coll London, Dept Life Sci, London SW7 2AZ, England

[2] Ecole Polytech Fed Lausanne EPFL, Inst Mat, CH-1015 Lausanne, Switzerland

[3] Imperial Coll London, Dept Infect Dis, London W2 1PG, England

[4] Imperial Coll London, Dept Mat, London SW7 2AZ, England

[5] Imperial Coll London, Dept Bioengn, London SW7 2AZ, England

[6] Imperial Coll London, Inst Biomed Engn, London SW7 2AZ, England

[7] Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden

[8] STFC, Rutherford Appleton Lab, ISIS Neutron & Muon Source, Didcot OX1 ODE, Oxon, England

[9] Ecole Polytech Fed Lausanne EPFL, Inst Bioengn, CH-1015 Lausanne, Switzerland

[10] Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia

来源：

ACS CENTRAL SCIENCE | 2022年 / 8卷 / 09期

基金：

瑞士国家科学基金会; 欧盟地平线“2020”; 英国工程与自然科学研究理事会; 英国惠康基金; 欧洲研究理事会;

关键词：

PLASMODIUM-FALCIPARUM MEROZOITES; ERYTHROCYTE INVASION; SULFATED GLYCOSAMINOGLYCANS; CORRELATION SPECTROSCOPY; MICRO-ASSAY; HEPARIN; NANOPARTICLES; MOLECULES; PLATFORM;

D O I：

10.1021/acscentsci.1c01368

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 nanopartides that mimic functional components of host cell membranes, yielding multivalent nano-mimics 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 comnavirus 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.

引用

页码：1238 / 1257

页数：20