Design Strategies for Cellular Nanosponges as Medical Countermeasures

The interest in using therapeutic nanoparticles to bind with harmful molecules or pathogens and subsequently neutralize their bioactivity has grown tremendously.Among various nanomedicine platforms,cell membrane-coated nanoparticles,namely,“cellular nanosponges,”stand out for their broadspectrum neutralization capability challenging to achieve in traditional countermeasure technologies.Such ability is attributable to their cellular function-based rather than target structure-based working principle.Integrating cellular nanosponges with various synthetic substrates further makes their applications exceptionally versatile and adaptive.This review discusses the latest cellular nanosponge technology focusing on how the structure–function relationship in different designs has led to versatile and potent medical countermeasures.Four design strategies are discussed,including harnessing native cell membrane functions for biological neutralization,functionalizing cell membrane coatings to enhance neutralization capabilities,combining cell membranes and functional cores for multimodal neutralization,and integrating cellular nanosponges with hydrogels for localized applications.Examples in each design strategy are selected,and the discussion is to highlight their structure–function relationships in complex disease settings.The review may inspire additional design strategies for cellular nanosponges and fulfill even broader medical applications.

Engineered Biomimetic Platelet Membrane-Coated Nanoparticles Block Staphylococcus aureus Cytotoxicity and Protect Against Lethal Systemic Infection

Staphylococcus aureus(S.aureus)is a leading human pathogen capable of producing severe invasive infections such as bacteremia,sepsis,and endocarditis with high morbidity and mortality,exacerbated by the increasingly widespread antibiotic resistance exemplified by methicillin-resistant strains(MRSA).S.aureus pathogenesis is fueled by the secretion of toxins—such as the membrane-damaging pore-forming atoxin,which have diverse cellular targets including the epithelium,endothelium,leukocytes,and platelets.Here,we examine the use of human platelet membrane-coated nanoparticles(PNPs)as a biomimetic decoy strategy to neutralize S.aureus toxins and preserve host cell defense functions.The PNPs blocked platelet damage induced by S.aureus secreted toxins,thereby supporting platelet activation and bactericidal activity.Likewise,the PNPs blocked macrophage damage induced by S.aureus secreted toxins,thus supporting macrophage oxidative burst,nitric oxide production,and bactericidal activity,and diminishing MRSA-induced neutrophil extracellular trap release.In a mouse model of MRSA systemic infection,PNP administration reduced bacterial counts in the blood and protected against mortality.Taken together,the results from the present work provide a proof of principle of the therapeutic benefit of PNPs in toxin neutralization,cytoprotection,and increased host resistance to invasive S.aureus infection.

Viral and nonviral nanocarriers for in vivo CRISPR-based gene editing

The continued development of clustered regularly interspaced short palindromic repeats(CRISPR)technology has the potential to greatly impact clinical medicine,particularly for disease diagnosis and treatment.Despite high demand for the in vivo delivery of CRISPR-based therapies,significant challenges persist.These include rapid degradation by enzymes,inefficient disease site targeting,and the risk of undesired off-target outcomes.Nanoparticulate platforms,with their tailorable properties,have been engineered to efficiently package CRISPR payloads in various formats,including as plasmid DNA,mRNA,and ribonucleoprotein complexes,for in vivo delivery.Among them,recombinant adeno-associated viruses,virus-like particles,and lipid nanoparticles have displayed exceptional promise.This review will discuss the development of these and other nanocarriers for in vivo CRISPR-based genome editing.

Recent Progress in Capturing and Neutralizing Inflammatory Cytokines

Inflammatory cytokines are key players in modulating immune responses to mount effective host defense.However,excessive production of inflammatory cytokines contributes to the destructive components responsible for various inflammatory disorders.As a result,treatment strategies have been developed to lower the cytokine levels or block their bioactivity.In particular,therapeutic agents that directly capture and neutralize cytokines have gained significant attention as they bypass the interactions with the host cells,and therefore,are less likely to induce immunogenic response and clearance.Among them,“monoplex”platforms such as cytokine-neutralizing antibodies(CNAs)are commonly designed to target a specific cytokine for neutralization.Meanwhile,to address the multiplexity of the cytokine targets in diseases,multiplex platforms such as glycosaminoglycan-containing biomaterials and cell-membrane-coated nanoparticles are emerging.Herein,we have reviewed the recent progress of these cytokine-neutralizing platforms(CNPs)and discussed their applications in treating inflammatory disorders.Overall,understanding the structure–function relationships underlying these CNPs would lead to the design of novel therapeutics toward effective management of inflammatory diseases.