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Updated: Jun 5, 2025

A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
Published on: December 23, 2016
Advances in acid-degradable and enzyme-cleavable linkers for drug delivery
Sheng Zhao1, Na Yu2, Hesong Han1
1Department of Bioengineering and Innovative Genomics Institute, University of California Berkeley, 2151 Berkeley Way, Berkeley, CA 94720, USA.
Abstract:
Drug delivery vectors have the potential to improve the efficacy of therapeutics, including small molecules and nucleic acid-based drugs. However, challenges remain in developing linkages that enable the precise and efficient release of therapeutic cargo in response to mildly acidic environments or lysosomal enzymes. This review highlights recent advances in acid-degradable acetal/ketal and enzyme-cleavable linkages for endolysosomal release. These innovations include the developments of azido-acetal linkers with improved stability and hydrolysis kinetics, organocatalytic trans-isopropenylation for synthesizing asymmetric ketals and their applications in drug delivery, and enzyme-cleavable linkers activated by cathepsin B or β-galactosidase.
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