期刊
NANOSCALE
卷 12, 期 28, 页码 15222-15235出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0nr02651d
关键词
-
类别
资金
- National Natural Science Foundation of China [30973645, 21707012]
- Chongqing Natural Science Foundation [cstc2017shmsA130028]
- Venture & Innovation Support Program for Chongqing Overseas Returnees [cx2018104]
- Research Program of Chongqing Municipal Education Commission [KJQN201902802, CYS19210]
The improvement and maintenance of enzymatic activities represent major challenges. However, to address these we developed novel biomimetic polysaccharide hyaluronan (Hn)-cloaked lipidic nanovesicles (BHLN) and microassemblies (BHLNM) as enzyme carriers that function by entrapping enzymes in the core or by tethering them to the inner/outer surfacesviacovalent interactions. The effectiveness of these enzyme carriers was demonstrated through an evaluation of the enzymatic activity and anti-hyperuricemia bioactivity of urate oxidase (also called uricase, Uase). We showed that Uase was effectively loaded within the BHLN/BHLNM (UHLN/UHLNM) and maintained good enzymatic bioactivity through a range of effects, including isolation from the external environment due to the vesicle-carrying (shielding effect), avoidance of recognition by the reticuloendothelial system due to Hn-cloaking (long-term effect), production of beneficial conformational changes (allosteric effect) due to a favorable internal microenvironment of construction and vesicle loading, and stabilization due to the reversible conjugation of Uase or vesicle and serum albumin (deposit effect). UHLN/UHLNM had significantly increased bioavailability (similar to 533% and similar to 331% compared to Uase) and demonstrated greatly improved efficacy, whereby the time required for UHLN/UHLNM to lower the plasma uric acid concentration to a normal level was much shorter than that for free Uase. The interactions of the therapeutic enzyme (Uase), biomimetic membrane components (Hn and phospholipid), and serum albumin were investigated with a fluorescent probe and computational simulations to help understand the superior properties of UHLN/UHLNM.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据