Journal
POLYMER JOURNAL
Volume 49, Issue 7, Pages 527-534Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/pj.2017.17
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Funding
- Japan Society for the Promotion of Science (JSPS) [16H05910]
- JSPS [26750155]
- Azuma Medical & Dental Research Grant
- Grants-in-Aid for Scientific Research [26750155, 16H05910] Funding Source: KAKEN
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Polyrotaxanes (PRXs), comprising many cyclic molecules threaded onto a linear polymer chain capped with bulky stopper molecules, have attracted considerable attention in the design of biomaterials. If cleavable linkages are included between the axle polymer terminals and bulky stopper molecules, PRXs acquire a stimuli-responsive dissociation ability. Such stimuli-cleavable PRXs can dissociate into their constituent molecules in response to various chemical and physical stimuli, such as the reductive intracellular environment and the acidic lysosomal environment. In this focus review, the basic principle of stimuli-cleavable PRX design and characteristics of stimuli-cleavable PRXs as drug delivery carriers are described. Additionally, recent progress in the use of beta-cyclodextrin-threaded stimuli-cleavable PRXs as a therapeutic agent for treating Niemann-Pick-type C (NPC) disease, a family of lysosomal storage disorders characterized by lysosomal accumulation of cholesterol, is described. The lysosomal release of threaded beta-cyclodextrins from PRXs leads to the formation of an inclusion complex with the cholesterols that accumulate in NPC disease, promoting extracellular excretion of cholesterols. Interestingly, these stimuli-cleavable PRXs improve impaired autophagic functions in NPC disease in addition to reducing cholesterol. Therefore, stimuli-cleavable PRXs are promising candidates for the treatment of intractable metabolic disorders.
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