Photo and redox dual-stimuli-responsive β-cyclodextrin-ferrocene supramolecules for drug delivery

Abstract

Amphiphilic photo and redox dual-stimuli-cleavable β-cyclodextrin-ferrocene supramolecules were synthesized through noncovalent interactions of ferrocene (Fc) and β-cyclodextrin (β-CD) born by 5-hydroxy-2-nitrobenzyl alcohol (ONB), a photodegradable linker between the β-CD and poly(4-substituted-ɛ-caprolactone) (PXCLn) chain. The terminal host–guest MPEG-Fc/β-CD-ONB-PXCLn complex can formed micelles in the aqueous phase. The critical micelle concentration ranged from 3.16 to 11.50 mg L−1. The drug-loading content and drug entrapment efficiency of the complex were lower than those of the parent β-CD. When exposed to ultraviolet irradiation and hydrogen peroxide, complex micelles could dissociate and efficiently release the loaded drug. Nanoparticles exhibited almost no toxicity at concentrations up to 1000 μg mL−1. The uptake of doxorubicin-incorporated micelles by HeLa cells was faster than that of free doxorubicin within the first 5 min. DOX-loaded MPEG45-Fc/β-CD-ONB-PMCL23 micelles effectively inhibited the proliferation of HeLa cells with a half maximal inhibitory concentration (IC50) of 3.8 µg mL−1.