New Insight into a Cancer Theranostic Probe: Efficient Cell-Specific Delivery of SN-38 Guided by Biotinylated Poly(vinyl alcohol)

Abstract

An optically modulated “turn-on” theranostic prodrug TP1 has been explored and formulated with biotinylated poly(vinyl alcohol) ( biotinPVA ) to obtain desired pharmacokinetics. TP1, consisting of the antineoplastic camptothecin analogue SN-38, and the fluorescent dye rhodol green have been covalently conjugated through a disulfide bond. Glutathione triggering the release of drug and fluorophore has been well established by UV–vis measurements through mass spectral analysis in physiological conditions. The biocompatible biotinPVA formulated prodrug ( PTP1 ) showed remarkably higher stability against blood serum and cell-specific activation in contrast to that of TP1 . Significantly, PTP1 permits monitoring of the delivery and release of well-known topoisomerase I inhibitor SN-38 by modulating fluorescence signal at λ em 550 nm within intracellular milieus. Moreover, theranostic probe PTP1 exhibited dose-dependent antiproliferative activity against receptor-positive HeLa cells, whereas it did not show such an effect against receptor-negative NIH3T3 cells. Finally, the cell-specific antiproliferative activity of PTP1 via the apoptotic pathway is an efficient approach in cancer theranostics. Thus, futuristic PTP1 could be a promising agent in which diagnostic and prognostic data will be monitored synergistically.