Journal
NANOTECHNOLOGY
Volume 32, Issue 14, Pages -Publisher
IOP PUBLISHING LTD
DOI: 10.1088/1361-6528/abd7b1
Keywords
pH; GSH; anticancer; beta-cyclodextrin
Funding
- National Natural Science Foundation of China [21576295]
- Scientific Research Fund of Hunan Provincial Education Department [19C0774]
- Natural Science Foundation of Hunan Province, China [2020JJ5156]
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The study utilizes methylated beta-cyclodextrins linked with acid-sensitive acylhydrazone and GSH-sensitive disulfide bonds to achieve precise drug release, with the potential for future clinical applications. In vivo studies show specific drug delivery characteristics and controlled drug release behaviors in tumor sites, leading to high antitumor activity and low toxicity. This dual stimuli-responsive bis(beta-CD) demonstrates superior amphiphilicity and biocompatibility, highlighting its great potential for clinical applications.
The intrinsic poor solubility and limited load capacity of beta-cyclodextrins (beta-CDs) results in reduced bioavailability, rendering the material unsuitable in complex biological environments. In this work, a pair of beta-CDs was methylated and covalently linked with acid-sensitive acylhydrazone and GSH-sensitive disulfide bonds to ensure a precise drug release pattern. The hydrophobic anticancer drug doxorubicin (Dox) was encapsulated inside the hydrophobic core of bis(beta-CD) via hydrophobic association with loading capacity of 24% in weight and a hydrodynamic size of about 100 nm. When exposed to acidic and reductive environments, the acylhydrazone and disulfide bonds were found to be cleaved, resulting in Dox release. Using fluorescence imaging and flow cytometry analysis, the designed bis(beta-CD) were determined to activate the drug release behavior by specific intracellular stimuli (pH and GSH). In vivo studies demonstrated specific drug delivery characteristics and controlled drug release behaviors in the tumor sites, giving rise to high antitumor activity and low toxicity. Taken in concert, this dual stimuli-responsive bis(beta-CD) with superior amphiphilicity and biocompatibility features showed great potential for future clinical applications.
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