Self-Assembled Nanovehicle for Intracellular Enzyme-Triggered Antitumor Drug Release
MACROMOLECULAR CHEMISTRY AND PHYSICS(2022)
Abstract
Enzyme-responsive and biocompatible supramolecular nanocarriers (NCs) have attracted intensive attention in the field of biomaterials, and have found many feasible applications, particularly for controlling drug-release at specific anchor sites where the enzyme is overexpressed. However, the introduction of specific enzyme-responsive sites in drug nanocarriers that can be enzymatically triggered to release drugs within tumor cells remains a challenge. In this manuscript, an enzyme-responsive supramolecular nanoparticle, (SBE)(7m)-beta-CD superset of PS NPs is successfully prepared, based on inducing aggregation of negatively charged cyclodextrin toward positively charged protein. The obtained nanoparticles showed trypsin-trigger disassemble behavior that is considered as drug vehicles to load antitumor drug celastrol (CSL). Furthermore, CSL-loaded NPs exhibit controlled release behavior of CSL in response to trypsin (TPS) stimulation. Notably, cell biology experiments reveal that loading CSL by (SBE)(7m)-beta-CD superset of PS NPs not only reduces cytotoxicity for normal cells but also presents a similar therapeutic effect of free CSL for five tumor cells. The obtained nanoparticle appears to hold practical potential for the controllable release of CSL in tumor cells.
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Key words
antitumor drug, cyclodextrin, enzyme responsiveness, supramolecular nanocarriers, targeted release
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