Cell-Membrane-Mimicking Nanodecoys against Infectious Diseases
Identifieur interne : 000004 ( Pmc/Corpus ); précédent : 000003; suivant : 000005Cell-Membrane-Mimicking Nanodecoys against Infectious Diseases
Auteurs : Lang Rao ; Rui Tian ; Xiaoyuan ChenSource :
- ACS Nano [ 1936-0851 ] ; 2020.
Abstract
Infectious diseases are a leading cause of mortality worldwide, with viruses and bacteria in particular having enormous impacts on global healthcare. One major challenge in combatting such diseases is a lack of effective drugs or specific treatments. In addition, drug resistance to currently available therapeutics and adverse effects caused by long-term overuse are both serious public health issues. A promising treatment strategy is to employ cell-membrane mimics as decoys to trap and to detain the pathogens. In this Perspective, we briefly review the infection mechanisms adopted by different pathogens at the cellular membrane interface and highlight the applications of cell-membrane-mimicking nanodecoys for systemic protection against infectious diseases. We also discuss the implication of nanodecoy–pathogen complexes in the development of vaccines. We anticipate this Perspective will provide new insights on design and development of advanced materials against emerging infectious diseases.
Url:
DOI: 10.1021/acsnano.0c01665
PubMed: 32129977
PubMed Central: 7094139
Links to Exploration step
PMC:7094139Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cell-Membrane-Mimicking
Nanodecoys against Infectious
Diseases</title><author><name sortKey="Rao, Lang" sort="Rao, Lang" uniqKey="Rao L" first="Lang" last="Rao">Lang Rao</name></author><author><name sortKey="Tian, Rui" sort="Tian, Rui" uniqKey="Tian R" first="Rui" last="Tian">Rui Tian</name></author><author><name sortKey="Chen, Xiaoyuan" sort="Chen, Xiaoyuan" uniqKey="Chen X" first="Xiaoyuan" last="Chen">Xiaoyuan Chen</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32129977</idno><idno type="pmc">7094139</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094139</idno><idno type="RBID">PMC:7094139</idno><idno type="doi">10.1021/acsnano.0c01665</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000004</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000004</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cell-Membrane-Mimicking
Nanodecoys against Infectious
Diseases</title><author><name sortKey="Rao, Lang" sort="Rao, Lang" uniqKey="Rao L" first="Lang" last="Rao">Lang Rao</name></author><author><name sortKey="Tian, Rui" sort="Tian, Rui" uniqKey="Tian R" first="Rui" last="Tian">Rui Tian</name></author><author><name sortKey="Chen, Xiaoyuan" sort="Chen, Xiaoyuan" uniqKey="Chen X" first="Xiaoyuan" last="Chen">Xiaoyuan Chen</name></author></analytic><series><title level="j">ACS Nano</title><idno type="ISSN">1936-0851</idno><idno type="eISSN">1936-086X</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p content-type="toc-graphic"><graphic xlink:href="nn0c01665_0002" id="ab-tgr1"></graphic></p><p>Infectious
diseases are a leading cause of mortality worldwide,
with viruses and bacteria in particular having enormous impacts on
global healthcare. One major challenge in combatting such diseases
is a lack of effective drugs or specific treatments. In addition,
drug resistance to currently available therapeutics and adverse effects
caused by long-term overuse are both serious public health issues.
A promising treatment strategy is to employ cell-membrane mimics as
decoys to trap and to detain the pathogens. In this Perspective, we
briefly review the infection mechanisms adopted by different pathogens
at the cellular membrane interface and highlight the applications
of cell-membrane-mimicking nanodecoys for systemic protection against
infectious diseases. We also discuss the implication of nanodecoy–pathogen
complexes in the development of vaccines. We anticipate this Perspective
will provide new insights on design and development of advanced materials
against emerging infectious diseases.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Cohen, M L" uniqKey="Cohen M">M. L. Cohen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Braden, C R" uniqKey="Braden C">C. R. Braden</name></author><author><name sortKey="Dowell, S F" uniqKey="Dowell S">S. F. Dowell</name></author><author><name sortKey="Jernigan, D B" uniqKey="Jernigan D">D. B. Jernigan</name></author><author><name sortKey="Hughes, J M" uniqKey="Hughes J">J. M. Hughes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pati, R" uniqKey="Pati R">R. Pati</name></author><author><name sortKey="Shevtsov, M" uniqKey="Shevtsov M">M. Shevtsov</name></author><author><name sortKey="Sonawane, A" uniqKey="Sonawane A">A. Sonawane</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, J T" uniqKey="Wu J">J. T. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">ACS Nano</journal-id><journal-id journal-id-type="iso-abbrev">ACS Nano</journal-id><journal-id journal-id-type="publisher-id">nn</journal-id><journal-id journal-id-type="coden">ancac3</journal-id><journal-title-group><journal-title>ACS Nano</journal-title></journal-title-group><issn pub-type="ppub">1936-0851</issn><issn pub-type="epub">1936-086X</issn><publisher><publisher-name>American
Chemical Society</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32129977</article-id><article-id pub-id-type="pmc">7094139</article-id><article-id pub-id-type="doi">10.1021/acsnano.0c01665</article-id><article-categories><subj-group><subject>Perspective</subject></subj-group></article-categories><title-group><article-title>Cell-Membrane-Mimicking
Nanodecoys against Infectious
Diseases</article-title></title-group><contrib-group><contrib contrib-type="author" id="ath1"><name><surname>Rao</surname><given-names>Lang</given-names></name></contrib><contrib contrib-type="author" id="ath2"><name><surname>Tian</surname><given-names>Rui</given-names></name></contrib><contrib contrib-type="author" corresp="yes" id="ath3"><name><surname>Chen</surname><given-names>Xiaoyuan</given-names></name><xref rid="cor1" ref-type="other">*</xref></contrib><aff id="AFF-d7e55-autogenerated">Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB),<institution>National Institutes of Health (NIH)</institution>, Bethesda, Maryland 20892,<country>United States</country></aff></contrib-group><author-notes><corresp id="cor1"><label>*</label>Email: <email>shawn.chen@nih.gov</email>.</corresp></author-notes><pub-date pub-type="epub"><day>04</day><month>03</month><year>2020</year></pub-date><pub-date pub-type="ppub"><day>24</day><month>03</month><year>2020</year></pub-date><volume>14</volume><issue>3</issue><fpage>2569</fpage><lpage>2574</lpage><history></history><permissions><copyright-statement>Copyright © 2020 U.S. Government</copyright-statement><copyright-year>2020</copyright-year><copyright-holder>U.S. Government</copyright-holder><license license-type="open-access"><license-p>This article is made available via the PMC Open Access Subset for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p></license></permissions><abstract><p content-type="toc-graphic"><graphic xlink:href="nn0c01665_0002" id="ab-tgr1"></graphic></p><p>Infectious
diseases are a leading cause of mortality worldwide,
with viruses and bacteria in particular having enormous impacts on
global healthcare. One major challenge in combatting such diseases
is a lack of effective drugs or specific treatments. In addition,
drug resistance to currently available therapeutics and adverse effects
caused by long-term overuse are both serious public health issues.
A promising treatment strategy is to employ cell-membrane mimics as
decoys to trap and to detain the pathogens. In this Perspective, we
briefly review the infection mechanisms adopted by different pathogens
at the cellular membrane interface and highlight the applications
of cell-membrane-mimicking nanodecoys for systemic protection against
infectious diseases. We also discuss the implication of nanodecoy–pathogen
complexes in the development of vaccines. We anticipate this Perspective
will provide new insights on design and development of advanced materials
against emerging infectious diseases.</p></abstract><custom-meta-group><custom-meta><meta-name>document-id-old-9</meta-name><meta-value>nn0c01665</meta-value></custom-meta><custom-meta><meta-name>document-id-new-14</meta-name><meta-value>nn0c01665</meta-value></custom-meta><custom-meta><meta-name>ccc-price</meta-name><meta-value></meta-value></custom-meta></custom-meta-group></article-meta><notes id="notes-d1e21-autogenerated"><fn-group><fn fn-type="" id="d30e116"><p>This article is made available for a limited time sponsored by ACS under the <ext-link ext-link-type="uri" xlink:href="http://pubs.acs.org/page/policy/freetoread/index.html">ACS Free to Read License</ext-link>, which permits copying and redistribution of the article for non-commercial scholarly purposes.</p></fn></fn-group></notes></front><body><p id="sec1">Infectious diseases have recently
emerged as a serious global public health concern, underscored by
the rapidly increasing number of drug-resistant strains of existing
pathogens and the emergence of new pathogens.<sup><xref ref-type="bibr" rid="ref1">1</xref>,<xref ref-type="bibr" rid="ref2">2</xref></sup> Collectively,
these pathogen infections cause millions of deaths and, thus, have
a huge impact on global healthcare and socioeconomical development.<sup><xref ref-type="bibr" rid="ref3">3</xref></sup> Very recently, the World Health Organization
(WHO) declared the outbreak of a novel corona virus disease (COVID-19),
in China a Public Health Emergency of International Concern.<sup><xref ref-type="bibr" rid="ref4">4</xref></sup> The new disease, first made public by Wuhan,
China at the end of December 2019, has already spread to 65 countries; the number of people in China infected
with COVID-19 reached 90,000 on 3 March 2020, and more than 3000 of
them have died.<sup><xref ref-type="bibr" rid="ref5">5</xref>,<xref ref-type="bibr" rid="ref6">6</xref></sup> The primary challenge in fighting
such emerging diseases is the lack of effective drugs or specific
treatments.<sup><xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref8">8</xref></sup> In addition, adverse side effects and increasing
drug resistances owing to long-term overuse are also serious issues.<sup><xref ref-type="bibr" rid="ref9">9</xref>,<xref ref-type="bibr" rid="ref10">10</xref></sup> New and effective prevention and treatment strategies need to be
developed urgently.</p><p>Pathogens, or disease-causing infection
agents, are all over the
world in which we live.<sup><xref ref-type="bibr" rid="ref11">11</xref>,<xref ref-type="bibr" rid="ref12">12</xref></sup> Although these microbes
can come in different forms, they all have one thing in common: to
cause infection, they must invade a host.<sup><xref ref-type="bibr" rid="ref13">13</xref>,<xref ref-type="bibr" rid="ref14">14</xref></sup> The cell membrane is one of the major barriers that pathogens need
to conquer.<sup><xref ref-type="bibr" rid="ref13">13</xref></sup> For example, a virus first
needs to attach itself to the cell membrane and then injects its genetic
material into the host cell prior to replication.<sup><xref ref-type="bibr" rid="ref15">15</xref></sup> Such structural similarity provides the opportunity to
develop new therapeutic platforms for broad-spectrum anti-infection
applications. Recent efforts have shown multiple anti-infection applications
by utilizing cell-membrane-based nanostructures.<sup><xref ref-type="bibr" rid="ref16">16</xref>−<xref ref-type="bibr" rid="ref19">19</xref></sup> These novel formulations take
advantage of the fact that, despite their different infection modes,
pathogens must interact with host cell membranes at some point. Furthermore,
biomimetic nanoparticles have many inherent properties that can benefit
anti-infection applications, including long systemic circulation and
multivalent pathogen interaction.<sup><xref ref-type="bibr" rid="ref20">20</xref>−<xref ref-type="bibr" rid="ref22">22</xref></sup></p><p>In light of these recent
advances, in this Perspective, we review
the evolution of cellular-membrane-based nanodecoys with a specific
focus on infectious-disease-related studies. We first discuss multiple
pathogen–membrane interactions to elucidate the fundamental
action mechanism of such biomimetic nanodecoys against pathogen infections.
We then provide an overview of the design and preparation of cell-membrane-mimicking
formulations as nanodecoys to trap and to detain pathogens. Finally,
we discuss the implication of utilizing nanodecoy–pathogen
complexes for vaccination. We believe this Perspective can provide
new insights on the development of new and effective prevention and
treatment strategies for infectious diseases.</p><sec id="sec2"><title>Pathogen–Membrane
Interactions</title><p>According to their morphology and structure,
pathogens can generally
be divided into four main categories: viruses, bacteria, fungi, and
parasites.<sup><xref ref-type="bibr" rid="ref23">23</xref></sup> Despite the diversity of pathogens,
one similarity they share is how they cause infectious disease: these
pathogens usually invade the host by interacting with the host cell
membrane first.<sup><xref ref-type="bibr" rid="ref13">13</xref></sup> Here, we briefly review
the interactions between different pathogens and hosts at the cell–membrane
interface.</p><p>Viruses are small infectious agents that do not grow
by cell division
but instead use the host metabolism to complete self-replication.
Viruses can infect all types of life forms on Earth, from animals
and plants to microorganisms. The modes of viral infection and replication
differ greatly between species, but attachment is the basic stage,
in which viral capsid proteins specifically bind to the receptors
on the host cellular membrane.<sup><xref ref-type="bibr" rid="ref8">8</xref></sup> For example,
HIV infects human leukocytes through the specific interaction between
its surface protein gp120 and the CD4 receptor and the CCR5 or CXCR4
co-receptors on CD4<sup>+</sup> T cells.<sup><xref ref-type="bibr" rid="ref24">24</xref></sup></p><p>Bacteria are one kind of biological cell that compose a wide
range
of prokaryotic microorganisms. The relationship between bacteria and
humans is complex. Sometimes bacteria offer us a helping hand. For
example, probiotics help us digest. In other cases, bacteria are subversive,
causing infectious diseases like methicillin-resistant <italic>Staphylococcus aureus</italic> (MRSA).<sup><xref ref-type="bibr" rid="ref25">25</xref></sup> Typically, pathogenic bacteria express and/or release a
large domain of molecules that target the host membrane and facilitate
many individual host responses.<sup><xref ref-type="bibr" rid="ref16">16</xref></sup> The molecular
mechanisms of the interactions between bacteria and hosts are different
across different species. For example, many Gram-positive pathogens
secrete pore-forming toxins that can form pores in the cell membranes
and lead to cell lysis, whereas Gram-negative pathogens secrete endotoxins
that can activate macrophages to produce inflammatory cytokines.<sup><xref ref-type="bibr" rid="ref26">26</xref></sup></p><p>A fungus is any member of eukaryotic organisms,
including mushrooms
and microorganisms such as molds and yeasts. According to their different
structures, sizes, surface properties, and ability to secrete pathogenicity
factors, fungi can attack host cells in different ways, including
membrane disruption by mechanical forces and membrane remodeling by
fungal lipases.<sup><xref ref-type="bibr" rid="ref27">27</xref></sup> In addition, Moyes <italic>et al.</italic> discovered that <italic>Candida albicans</italic> is able to produce a peptide toxin that can directly damage host
membranes and activate host immunity.<sup><xref ref-type="bibr" rid="ref28">28</xref></sup></p><p>Parasitism is a relationship between different species in
evolutionary
biology, where one life form, the parasite, lives on or in another
life form, the host. Although the parasite may cause the host some
harm, the host is adapted structurally to live with the parasite.
For example, to complete their life cycle in the blood circulation,
the malaria parasite produces merozoite that can attach to and enter
into red blood cells (RBCs) where the parasite asexually divides to
form many copies of itself. The parasite copy then exits the infected
RBC and infects more RBCs.<sup><xref ref-type="bibr" rid="ref29">29</xref></sup></p></sec><sec id="sec3"><title>Trapping and
Detention of Pathogens with Nanodecoys</title><p>Due to the close interactions
between pathogens and cell membranes,
various cell-membrane-mimicking nanostructures have been employed
as decoys to mitigate pathogen infection.<sup><xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref26">26</xref>,<xref ref-type="bibr" rid="ref30">30</xref></sup> In the following
section, we review previous infectious disease research involving
cell-membrane mimics, with a special emphasis on the platforms developed
for pathogen trap and detention.</p><sec id="sec3.1"><title>Liposomes</title><p>Liposomes are artificial vesicles composed
of one or more hydrophobic phospholipid bilayers; they have been used
extensively for systemic delivery of therapeutic compounds. Because
liposomes imitate the capabilities of cell membranes in several ways,
they have been widely utilized as model membranes to study the infection
mechanisms of many pathogens at the biomembrane interface (<xref rid="fig1" ref-type="fig">Figure <xref rid="fig1" ref-type="fig">1</xref></xref>a).<sup><xref ref-type="bibr" rid="ref31">31</xref></sup> Research on the interaction between pathogens and liposomes
can be traced back to the 1960s, when Bangham <italic>et al.</italic> found that streptolysin-S is able to regulate the cationic permeability
of multilayer liposomes.<sup><xref ref-type="bibr" rid="ref32">32</xref></sup> Following the
early mechanistic studies, researchers further applied liposomes as
pathogen substrates in the emerging infectious disease area. For example,
liposome microarrays can be used for ultrasensitive detection of various
types of pathogens including viruses, bacteria, and fungi.<sup><xref ref-type="bibr" rid="ref33">33</xref></sup> These cell-membrane mimics, consisting of synthetical
lipids along with functional ligands, promote the formation of pathogen–liposome
complexes that effectively improve the detection sensitivity in various
electrochemical and immunological assays. Another example that utilizes
the liposome–pathogen interaction is direct inhibition of the
pathogen infection with liposomes. The pathogens were trapped and
detained by cell-membrane-mimicking liposomes, thereby preventing
them from attacking their cellular targets.<sup><xref ref-type="bibr" rid="ref34">34</xref></sup> In viral and bacterial infection models, treatment with functionalized
liposomes was demonstrated to improve subject survival as well as
to reduce the overall infection.<sup><xref ref-type="bibr" rid="ref34">34</xref>,<xref ref-type="bibr" rid="ref35">35</xref></sup> Engineered
liposomes have also been used as a secondary therapeutic to supplement
traditional anti-infective drugs. Systemic administration of nanoscale
liposomes along with penicillin effectively protected animals from <italic>S. pneumoniae</italic>- and <italic>S. aureus</italic>-caused septicemia.<sup><xref ref-type="bibr" rid="ref36">36</xref></sup> Moreover, researchers
have also exploited the liposome–pathogen interaction for infection-triggered
drug release. Motivated by targeting therapeutic drugs to the specific
site, pore-forming toxins are able to bore holes on the synthetic
liposomal vehicles, resulting in the selective release of vancomycin
at the infection sites.<sup><xref ref-type="bibr" rid="ref37">37</xref></sup> Surface engineering
of liposomes with specific molecules may further promote the applicability
of synthetic liposomes against infectious diseases. Magee <italic>et al.</italic>, for instance, successfully modified liposomes with
antiviral antibodies for effective protection against coxsackie A-21
virus infection.<sup><xref ref-type="bibr" rid="ref38">38</xref></sup> With the rapid developments
of biotechnology and nanotechnology, the physical and chemical properties
of phospholipid bilayers may be tuned finely to improve their efficacy
in various anti-infection applications.</p><fig id="fig1" position="float"><label>Figure 1</label><caption><p>Trapping and detention
of pathogens/toxins with nanodecoys. (a)
Artificial liposomes sequester bacterial exotoxins and rescue mice
from septicemia. Reprinted with permission from refs (<xref ref-type="bibr" rid="ref16">16</xref>) (copyright 2015 Elsevier
B.V.) and (<xref ref-type="bibr" rid="ref34">34</xref>) (copyright
2015 Nature Publishing Group). (b) Modified reconstituted high-density
lipoproteins (rHDL) effectively inhibit the cholera toxin attachment
to epithelial cells and prevent toxin-associated negative outcomes.
Reprinted with permission from ref (<xref ref-type="bibr" rid="ref41">41</xref>). Copyright 2010 American Society for Biochemistry
& Molecular Biology. (c) Cell-membrane-coated nanodecoys (NDs)
effectively trap Zika virus (ZIKV) and mitigate the ZIKV-caused fetal
microcephaly <italic>in vivo</italic>. Reprinted from ref (<xref ref-type="bibr" rid="ref17">17</xref>). Copyright 2019 American
Chemical Society.</p></caption><graphic xlink:href="nn0c01665_0001" id="gr1" position="float"></graphic></fig></sec><sec id="sec3.2"><title>Reconstituted Lipoproteins</title><p>In addition to liposomes,
reconstituted lipoproteins have also been extensively employed in
the development of anti-infection decoys. Lipoproteins are inherently
present in the human body as a disk-like patch of phospholipids bound
by apolipoproteins. By using their constructing ingredients, these
proteins can be controllably reconstituted.<sup><xref ref-type="bibr" rid="ref39">39</xref></sup> This method promises the controllable functionalization of lipoprotein
components at the molecular level, opening the door for any lipid-compatible
ingredients to be incorporated into the lipoprotein nanostructure.
Proton pumps, signaling proteins, and membrane-associating enzymes
have all been integrated into the reconstituted lipoproteins.<sup><xref ref-type="bibr" rid="ref39">39</xref></sup></p><p>Engineered lipoproteins have been demonstrated
to interact frequently with pathogens, leading to the effective suppression
of pathogen infectivity. This inhibition can be ascribed to the lipoproteins’
microdomains, which are also rich in pathogen/toxin receptors such
as sphingomyelin and cholesterol.<sup><xref ref-type="bibr" rid="ref40">40</xref></sup> Furthermore,
to develop anti-infection nanostructures for clinical use, Bricarello <italic>et al.</italic> prepared reconstituted high-density lipoprotein (rHDL)
to integrate ganglioside GM1 to improve affinity to certain pathogenic
molecules (<xref rid="fig1" ref-type="fig">Figure <xref rid="fig1" ref-type="fig">1</xref></xref>b).<sup><xref ref-type="bibr" rid="ref41">41</xref></sup> The modified rHDL effectively inhibited
the cholera toxin attachment to epithelial cells and prevented toxin-associated
negative outcomes. Although promising, further work along the lines
of how to alleviate the toxicity of such nanostructures and how to
improve the rHDL–host interaction is necessary before successful
translation of rHDL as an anti-infection candidate.</p></sec><sec id="sec3.3"><title>Cell-Membrane-Derived
Nanostructures</title><p>Cell-membrane-derived
nanoparticles present an attractive platform for anti-infection applications
because pathogens have evolved to utilize abundant molecules on the
cell membrane.<sup><xref ref-type="bibr" rid="ref42">42</xref></sup> Although synthetic liposomes
can be straightforwardly functionalized with specific ligands, it
has proven difficult to replicate or to mimic the complicated protein
compositions and functions in natural cell membranes. Natural cell-membrane-derived
vesicles possess a unique advantage of maintaining most of the natural
compositions and functions of source cell membranes, thereby enabling
each platform to exhibit properties that would otherwise be hard to
accomplish.<sup><xref ref-type="bibr" rid="ref43">43</xref>,<xref ref-type="bibr" rid="ref44">44</xref></sup> Moreover, emerging genetic editing
technology can be further employed to amend the antigen profile of
natural cellular membranes to fit different purposes.<sup><xref ref-type="bibr" rid="ref18">18</xref></sup></p><p>To develop biomimetic anti-infection nanodecoys, de Carvalho <italic>et al.</italic> demonstrated that CD4<sup>+</sup> T-cell-derived
exosomes could efficiently suppress HIV-1 infection <italic>in vitro</italic>.<sup><xref ref-type="bibr" rid="ref45">45</xref></sup> These exosomes exhibited the same
completed membrane protein composition as their source CD4<sup>+</sup> T cells, ensuring that they attached effectively to HIV-1, thereby
preventing the HIV-1 from binding to and entering healthy CD4<sup>+</sup> T cells. In addition, exosomes released from certain host
cells have also been utilized to suppress bacterial and parasitic
invasion of specific host cells, as well.<sup><xref ref-type="bibr" rid="ref46">46</xref></sup></p><p>Because many exotoxins secreted by bacteria and fungi are
known
for their unique capability to lyse erythrocytes (RBCs), RBC-derived
nanovesicles have been widely employed as a model to examine the kinetics
of these exotoxins.<sup><xref ref-type="bibr" rid="ref47">47</xref></sup> After removal of
the intracellular contents, these cell-membrane-derived nanovesicles
inherit the lipids, glycans, and proteins from their source cells,
enabling the pathogen–nanoparticle interaction to occur in
a natural manner.</p><p>In developing a biomimetic formulation that
traps exotoxins secreted
by bacteria, Hu <italic>et al.</italic> demonstrated that poly(lactic-<italic>co</italic>-glycolic acid) (PLGA) nanoparticles camouflaged with
RBC membranes are able to serve as toxin “nanosponges”,
absorbing pore-forming toxins and diverting them away from their intended
targets.<sup><xref ref-type="bibr" rid="ref26">26</xref></sup> Moreover, Rao <italic>et al.</italic> showed that mosquito host-cell-membrane-wrapped nanodecoys effectively
trap Zika virus (ZIKV) and divert it away from its healthy cellular
targets (<xref rid="fig1" ref-type="fig">Figure <xref rid="fig1" ref-type="fig">1</xref></xref>c).<sup><xref ref-type="bibr" rid="ref17">17</xref></sup> In mouse models, the research team further demonstrated
that these nanodecoys successfully mitigate the ZIKV-caused inflammatory
responses and fetal microcephaly. Compared to cell-membrane-derived
vesicles, the cell-membrane-coated nanostructures are not prone to
membrane fusion and therefore do not transfer detained pathogens to
host cells.<sup><xref ref-type="bibr" rid="ref48">48</xref>,<xref ref-type="bibr" rid="ref49">49</xref></sup> In addition, due to the core–shell
structure, the lipid membrane shell is stabilized by the nanoparticle
core, benefiting <italic>in vivo</italic> applications.<sup><xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref50">50</xref></sup></p></sec></sec><sec id="sec4"><title>Nanodecoy–Pathogen Complex for Vaccination</title><p>Considering
that cell-membrane-mimicking nanodecoys are able to
trap pathogens in a natural manner, the obtained nanoparticle–pathogen
complexes can be applied to develop vaccines.<sup><xref ref-type="bibr" rid="ref21">21</xref></sup> Typically, vaccine preparation relies on heat or chemical treatments
to destruct the protein’s tertiary structure, leading to antigen
alteration and reduced immunogenicity.<sup><xref ref-type="bibr" rid="ref51">51</xref></sup> However, the inherent balance between efficacy and safety presents
a great limitation to vaccine development. Recently, more efforts
have focused on weakening a pathogen’s infectivity while maintaining
its original structure, thus enhancing both the efficacy and safety
of vaccines.<sup><xref ref-type="bibr" rid="ref3">3</xref></sup> Trapping and detention of
pathogens/exotoxins by nanodecoys offer the chance to denude the pathogens’
infectious capabilities without compromising immunogenicity. Demonstrating
a novel concept of pathogen/toxin sequestration by cell-membrane-mimicking
nanodecoys for vaccination, Hu <italic>et al.</italic> showed that
the spontaneous interactions between RBC membrane-coated nanodecoys
and pore-forming toxins presented a facile approach for developing
safe and effective vaccines.<sup><xref ref-type="bibr" rid="ref21">21</xref></sup> The nanoparticle
vehicles are endowed with many properties that are beneficial to antigen
processing: the pathogens/toxins were displayed on immune cells in
their native manner; the nanoparticles’ small size and long
circulation promoted antigen presentation; and the nanoparticle carriers
were primarily absorbed by cells through endocytosis, thereby promoting
the localization and metabolism of pathogens/exotoxins in endolysosomal
sections. These properties together contributed to the improved safety
and efficiency by nanoparticle-trapped pathogens/toxins.</p></sec><sec id="sec5"><title>Conclusions and Outlook</title><p>Conventional
anti-infection strategies primarily depend on structure-customized
platforms such as antibodies and antisera. Although effective, these
formulations often require accurate identification of the pathogenic
species and have proven to be impractical to administer at times.
Amidst the increasing awareness of emerging virus epidemics as well
as the rising threat of drug-resistant bacteria, broadly applicable
platforms have tremendous potential for the treatment of infectious
diseases. In-depth biological research has elucidated different mechanisms
of pathogen infection, most of which involve attaching to the cellular
membrane biointerface and invading the host cells. Recent nanotechnology
developments have resulted in a variety of nanoscale cell-membrane-mimicking
formulations, including liposomes, reconstituted lipoproteins, and
cell-membrane nanostructures. Much effort has been directed toward
exploring the interactions between these biomimetic nanodecoys and
pathogens/exotoxins, and researchers have demonstrated successful
protection against major pathogenic infections through nanoparticle
functionalization.<sup><xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref26">26</xref>,<xref ref-type="bibr" rid="ref30">30</xref></sup> These nanoformulations can be infused <italic>in vivo</italic> to alleviate the disease burden in multiple infectious
diseases. Moreover, pathogen/toxin trapping and detention by cellular-membrane-based
nanostructures have wider implications in the development of safe
and effective vaccines.<sup><xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref21">21</xref></sup></p><p>Cell-membrane-mimicking
nanodecoys represent a promising technology
that has enormous translation potential.<sup><xref ref-type="bibr" rid="ref16">16</xref></sup> To realize this potential, further exploration and detailed study
are required. Scalability is a crucial factor that is required for
any clinical translational nanostructures. Previous work on the robust
preparation of liposomes, lipoproteins, and cell-membrane nanoparticles
indicates the need for further explorations on the large-scale production
of these biomimetic nanodecoys.<sup><xref ref-type="bibr" rid="ref17">17</xref></sup> Moving
forward, the host–pathogen affinity is a key issue that needs
to be further considered. For many pathogens with clear infection
mechanisms, strategies including bioconjugate chemistry and genetic
editing can be employed to enhance the specific protein expression,
resulting in enhanced platform efficacy.<sup><xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref52">52</xref></sup> A promising property of these bioinspired nanodecoys is that they
are highly customizable, especially for cell-membrane-coated nanoparticles.
Although most of the previous designs employed a PLGA nanoparticle
as the core, it is easy to imagine such cell-membrane-coated platforms
can be formed with many other types of nanoparticle cores,<sup><xref ref-type="bibr" rid="ref43">43</xref>,<xref ref-type="bibr" rid="ref47">47</xref>,<xref ref-type="bibr" rid="ref53">53</xref>−<xref ref-type="bibr" rid="ref55">55</xref></sup> such as magnetic
nanoparticles. With an additional magnet, cell-membrane-wrapped magnetic
particles can be localized to targeted sites and away from susceptible
tissues.<sup><xref ref-type="bibr" rid="ref54">54</xref></sup> Finally, although nanoparticle-trapped
pathogens have many advantages over traditional vaccine developments,
the nanocomplexes containing nondenatured pathogens unavoidably increase
safety risks. Further in-depth studies are needed prior to successful
clinical translation of these novel nanotechnologies.</p></sec></body><back><notes notes-type="COI-statement" id="notes1"><p>The authors
declare no competing financial interest.</p></notes><ack><title>Acknowledgments</title><p>We would like to thank Prof. Liangfang Zhang
at
University of California, San Diego, for manuscript discussion and
editing. This work was supported by the Intramural Research Program,
National Institute of Biomedical Imaging and Bioengineering (NIBIB),
National Institutes of Health (NIH).</p></ack><ref-list><title>References</title><ref id="ref1"><mixed-citation publication-type="journal" id="cit1"><name><surname>Cohen</surname><given-names>M. L.</given-names></name><article-title>Changing
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