4.8 Article

Screening of Zwitterionic Liposomes with Red Blood Cell-Hitchhiking and Tumor Cell-Active Transporting Capability for Efficient Tumor Entrance

期刊

ADVANCED FUNCTIONAL MATERIALS
卷 33, 期 16, 页码 -

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.202214369

关键词

liposomes; tertiary amine oxide; transcytosis; tumor penetration; zwitterionic lipids

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A type of tertiary amine oxide (TAO)-containing zwitterionic liposomal nanocarriers has been developed to hitchhike red blood cells (RBCs) to tumor blood vessels and enter solid tumors through transcytosis. Two types of TAO liposomes (TAOLs) have been identified that can induce efficient tumor cell transcytosis through rapid macropinocytosis and endoplasmic reticulum/Golgi-involved exocytosis. These zwitterionic TAOLs can hitchhike RBCs to gain long blood circulation and effectively enter and infiltrate the whole tumor through transcytosis. Chemotherapeutic drug-loaded liposomes have shown superior antitumor activity compared to traditional liposomal drugs.
The active transport of nanoparticles into the solid tumor through cell transcytosis has shown great promise in cancer nanomedicine, but it is challenging to develop efficient active transporting nanomedicines with the potential for clinical translation. Here, a type of tertiary amine oxide (TAO)-containing zwitterionic liposomal nanocarriers is developed that can hitchhike red blood cells (RBCs) to tumor blood vessels and enter solid tumors through transcytosis. To boost the active-transporting capability, a library of the TAO liposomes (TAOLs) with different chemical structures and particle sizes is constructed and screened by their stability and active transporting capability. Two types of TAOLs are identified that can induce efficient tumor cell transcytosis through rapid macropinocytosis and endoplasmic reticulum/Golgi-involved exocytosis. It is found that these zwitterionic TAOLs can hitchhike RBCs to gain long blood circulation, get off the cell at the tumor site, effectively enter the tumor through transcytosis, and infiltrate the whole tumor. The chemotherapeutic drug-loaded liposomes can stop the tumor progression of mice bearing human hepatocellular carcinoma HepG2 cells, exhibiting superior antitumor activity compared to the traditional liposomal drug. This study demonstrates a strategy to construct effective active transporting liposomal nanomedicines for efficient tumor entrance.

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