Enhanced targeted cytotoxic and apoptotic effects of docetaxel by enzyme-mediated controlled release system based on...

A novel system has been developed for the controlled release of docetaxel (DTX), an anticancer agent, utilizing β-cyclodextrin (β-CD) and maltogenic amylase (MAase) as the cyclodextrinase (CDase). In this study, we describe the creation of a targeted drug delivery system by conjugating MAase to a glutamate-urea-lysine (EUK) mimetic dipeptide, which acts as a ligand specific to the prostate-specific membrane antigen (PSMA), a crucial target for prostate cancer treatment. The conjugation of MAase and EUK was facilitated by dextran, as confirmed by dynamic light scattering (DLS). Additionally, we prepared a β-CD-DTX inclusion complex, which was validated using UV-visible (UV-vis) and Fourier-transform infrared (FT-IR) spectroscopy, resulting in an encapsulation efficiency of 31.43. In vitro studies indicated that the β-CD-DTX/MAase-EUK bioconjugate displayed enhanced cytotoxicity against LNCaP cells, which express high levels of PSMA, with a half-maximal inhibitory concentration (IC₅₀) of 34 nM after 48 h significantly lower than the 60 nM IC₅₀ associated with the β-CD-DTX/MAase system. Flow cytometric analysis revealed that the bioconjugate notably increased apoptotic rates compared to alternative formulations, showing early apoptosis at 28.2 % and late apoptosis at 14.2 %. Furthermore, activation of caspase-3/7 was significantly heightened in LNCaP cells treated with the β-CD-DTX/MAase-EUK system. These results indicate that the targeted delivery system enhances the solubility and bioavailability of DTX, thereby improving its therapeutic efficacy against prostate cancer while mitigating systemic toxicity.