Neutrophil-targeted liposomal platform: A shift in novel approach for early detection and treatment of cancer metastasis  

作　　者：Cong Li Kexin Zhang Zehua Cheng Lihong Wang Zehao Li Chao Shen Zhihang Li Zeyu Wang Lianrui Cao Lijiang Chen 

机构地区：[1]School of Pharmaceutical Science,Liaoning University,Shenyang 110036,China [2]Liaoning Key Laboratory of New Drug Research&Development,Shenyang 110036,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2024年第5期182-201,共20页亚洲药物制剂科学（英文）

基　　金：This work was supported by the Doctoral Start-up Foundation of Liaoning Province of China[Grant Number 2023-BS-086];the Fundemental Research Funds for Public Universitiesin Liaoning(LJKJT202402);the Youth Project of Liaoning Provincial Department of Education(JYTQN2023188);the Youth Scientific Research Fund Project of Liaoning University.

摘　　要：Tumormetastasis is responsible for 90%of cancer-associated deaths,and its early detection may decrease the likelihood of mortality.Studies have demonstrated that metastasis results from the interaction between“seeds”(tumor cells)and“soil”(pre-metastatic niche,PMN).As the first and most abundant immune cells to be recruited to PMN,neutrophils play a key role in the ultimate formation of metastatic foci through mechanisms such as supporting tumor cell growth,promoting angiogenesis,and shaping an immune-suppressive microenvironment.In this study,two distinct types of sialic acid(SA)-modified liposomes were prepared to target and regulate pro-metastatic neutrophils through the l-selectin receptor.One of these liposomes,named ICG@SAL,was used to encapsulate indocyanine green(ICG)and was specifically designed for the early detection of cancer metastasis.The other liposome,referred to as ABE/Cur@SAL,co-loaded abemaciclib(ABE)and curcumin(Cur),with the intention of suppressing the progression of metastatic tumor.Fluorescence imaging results from the mouse spontaneous metastasis model indicated that ICG@SAL demonstrated faster targeting and stronger accumulation in the metastatic organs than unmodified ICG liposomes(ICG@CL).This suggested that ICG@SAL could detect tumor metastasis at an early stage.The therapy with co-loaded liposomes in the mouse experimental lung metastasis model indicated that ABE/Cur@SAL could inhibit regulatory T(Treg)cell proliferation,enhance effector T cell activity and reduce tumorigenic factor release,implying that ABE/Cur@SAL could inhibit tumor metastasis.Overall,our work provided a sensitive and convenient approach to early diagnosis and treatment of tumor metastasis.ICG@SAL could be employed for the early detection of tumor metastasis,while ABE/Cur@SAL could be used to inhibit the development of tumor metastasis when early metastasis was identified.

关 键 词：Lung metastasis Early depletion LIPOSOME NEUTROPHIL Sialic acid Pre-metastatic niche 

分 类 号：R943[医药卫生—药剂学]