Reversibly crosslinked nanocarriers for on-demand drug delivery in cancer treatment

Yu Shao, Wenzhe Huang, Changying Shi, Sean T. Atkinson, Juntao Luo

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Polymer micelles have proven to be one of the most versatile nanocarriers for anticancer drug delivery. However, the in vitro and in vivo stability of micelles remains a challenge due to the dynamic nature of these self-assembled systems, which leads to premature drug release and nonspecific biodistribution in vivo. Recently, reversibly crosslinked micelles have been developed to provide solutions to stabilize nanocarriers in blood circulation. Increased stability allows nanoparticles to accumulate at tumor sites efficiently via passive and/or active tumor targeting, while cleavage of the micelle crosslinkages, through internal or external stimuli, facilitates on-demand drug release. In this review, various crosslinking chemistries as well as the choices for reversible linkages in these nanocarriers will be introduced. Then, the development of reversibly crosslinked micelles for on-demand drug release in response to single or dual stimuli in the tumor microenvironment is discussed, for example, acidic pH, reducing microenvironment, enzymatic microenvironment, photoirradiation and the administration of competitive reagents postmicelle delivery.

Original languageEnglish (US)
Pages (from-to)1409-1427
Number of pages19
JournalTherapeutic Delivery
Issue number12
StatePublished - Dec 2012
Externally publishedYes

ASJC Scopus subject areas

  • Pharmaceutical Science


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