【摘 要】
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Although multifarious tumor-targeting modifications of nanoparticulate systems have been at-tempted in joint efforts by our predecessors,it remains challenging for nanomedicine to traverse physiolog-ical barriers involving blood vessels,tissues,and cell b
【机 构】
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State Key Laboratory of Natural Medicines,Jiangsu Key Laboratory of Bioactive Natural Product Resear
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Although multifarious tumor-targeting modifications of nanoparticulate systems have been at-tempted in joint efforts by our predecessors,it remains challenging for nanomedicine to traverse physiolog-ical barriers involving blood vessels,tissues,and cell barriers to thereafter demonstrate excellent antitumor effects.To further overcome these inherent obstacles,we designed and prepared mycoplasma membrane(MM)-fused liposomes(LPs)with the goal of employing circulating neutrophils with the advantage of in-flammatory cytokine-guided autonomous tumor localization to transport nanoparticles.We also utilized in vivo neutrophil activation induced by the liposomal form of the immune activator resiquimod(LPs-R848).Fused LPs preparations retained mycoplasma pathogen characteristics and achieved rapid recogni-tion and endocytosis by activated neutrophils stimulated by LPs-R848.The enhanced neutrophil infiltration in homing of the inflammatory tumor microenvironment allowed more nanoparticles to be delivered into solid tumors.Facilitated by the formation of neutrophil extracellular traps(NETs),podophyllotoxin(POD)-loaded MM-fused LPs(MM-LPs-POD)were concomitantly released from neutrophils and subse-quently engulfed by tumor cells during inflammation.MM-LPs-POD displayed superior suppression effi-cacy of tumor growth and lung metastasis in a 4T1 breast tumor model.Overall,such a strategy of pathogen-mimicking nanoparticles hijacking neutrophils in situ combined with enhanced neutrophil infiltra-tion indeed elevates the potential of chemotherapeutics for tumor targeting therapy.
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