Engineering of Biocompatible pH-Responsive Nanovehicles from Acetalated Cyclodextrins as Effective Delivery Systems for Tumor Therapy

There is still an unmet demand for materials with excellent biocompatibility, controlled hydrolytic capability, and elegant responsiveness to chemical or physical stimuli. To engineer biocompatible materials from beta-cyclodextrin (beta-CD), in this study, we synthesized acetalated beta-CDs (Ac-beta CDs) by one-pot acetalation using 2-ethoxypropene as an acetonation reagent, which can be further processed into nanoparticles (NPs) via the emulsion technique. Ac-beta CD NPs showed pH-labile hydrolysis and pH-triggered release of docetaxel (DTX) payload. Both properties were mainly dominated by the molar ratio of linear to cyclic acetal, which can be conveniently modulated by the acetalation time used for materials synthesis. Ac-beta CD NPs were found to be biocompatible in both in vitro cell culture and in vivo acute toxicity evaluations following intravenous injection. In vitro cell culture experiments demonstrated that antitumor activity of DTX against both sensitive and resistant cancer cells was remarkably improved by formulation into Ac-beta CD nanomedicines. In vivo antitumor study also substantiated the dramatically enhanced efficacy of DTX/Ac-beta CD NPs in a melanoma-bearing nude mouse model. These studies demonstrated that NPs derived from Ac-beta CDs may serve as biocompatible and effective carriers for drug delivery.