Enhanced tumor homing of pathogen-mimicking liposomes driven by R848 stimulation:A new platform for synergistic oncology therapy

• 作者: Xiaobei Cheng Pei Yu Xiang Zhou Jiale Zhu Yubao Han Chao Zhang Lingyi Kong
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2022,（2）
• 所属期刊栏目: Original articles
• 页码范围: 924-938
• 页数: 15页
• 语种: 英文

摘要

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.