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Locked Nucleic Acid Nanomicelle with Cell-Penetrating Peptides for Glutathione-Triggered Drug Release and Cell Fluorescence Imaging.

Herein, we constructed a multifunctional spherical nanomicelle drug delivery system to improve the efficiency of cell uptake. The paclitaxel (PTX)-locked nucleic acid (LNA) monomer and the carboxyfluorescein (FAM)-labeled DNA were mixed together to assemble and form a spherical nanomicelle that was functionalized with transactivator of transcription (TAT), a cell-penetrating peptides (CPPs). A bioreductively activated disulfide was used to link the hydrophobic PTX to the LNA, allowing the PTX to be released freely in the presence of glutathione (GSH) upon cell uptake. Based on magnetic separation, the synthetic process of PTX-LNA monomers avoids time-consuming and labor-intensive shortcomings. Cellular uptake of PTX-LNA-TAT nanomicelle and the drug release occur rapidly as proved by fluorescence microscopy and flow cytometry. The resulting nanomicelle was greater stability, monodisperse size, and the high therapeutic potential. Furthermore, the system can readily achieve detection of GSH in the cancer cells. The detection limit for commercial GSH determined was 1.0 × 10-9 M by using PTX/Fluorescein isothiocyanate (FITC)-LNA/black hole quencher 1 (BHQ-1) as a probe.