淋巴系统
淋巴
淋巴管
体内
K8644湾
离体
生物
医学
病理
内科学
兴奋剂
受体
转移
生物技术
癌症
作者
Lauren F. Sestito,Kim To,Matthew T. Cribb,Paul A. Archer,Susan N. Thomas,J. Brandon Dixon
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-02-24
卷期号:9 (8)
被引量:2
标识
DOI:10.1126/sciadv.abq0435
摘要
Dysfunction of collecting lymphatic vessel pumping is associated with an array of pathologies. S-(-)-Bay K8644 (BayK), a small-molecule agonist of L-type calcium channels, improves vessel contractility ex vivo but has been left unexplored in vivo because of poor lymphatic access and risk of deleterious off-target effects. When formulated within lymph-draining nanoparticles (NPs), BayK acutely improved lymphatic vessel function, effects not seen from treatment with BayK in its free form. By preventing rapid drug access to the circulation, NP formulation also reduced BayK's dose-limiting side effects. When applied to a mouse model of lymphedema, treatment with BayK formulated in lymph-draining NPs, but not free BayK, improved pumping pressure generated by intact lymphatic vessels and tissue remodeling associated with the pathology. This work reveals the utility of a lymph-targeting NP platform to pharmacologically enhance lymphatic pumping in vivo and highlights a promising approach to treating lymphatic dysfunction.
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