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

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• 作者：Debabrata Dutta ; Susan M. Alex ; Kondapa Naidu Bobba ; Kaustabh Kumar Maiti ; Sankarprasad Bhuniya
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2016
• 出版时间：December 14, 2016
• 年：2016
• 卷：8
• 期：49
• 页码：33430-33438
• 全文大小：542K
• ISSN：1944-8252

文摘

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.