The design of drug delivery systems capable of minimal endolysosomal trapping, controlled drug release, and real-time monitoring of drug effect is highly desirable for personalized medicine. Herein, by using mesoporous silica nanoparticles (MSNs) coated with cell-penetrating poly(disulfide)s and a fluorogenic apoptosis-detecting peptide (DEVD-AAN), we have developed a platform that could be uptaken rapidly by mammalian cells via endocytosis-independent pathways. Subsequent loading of these MSNs with small molecule inhibitors and antisense oligonucleotides resulted in intracellular release of these drugs, leading to combination inhibition of endogenous miR-21 activities which was immediately detectable by the MSN surface-coated peptide using two-photon fluorescence microscopy.
Keywords: cell-penetrating poly(disulfide); drug delivery; endocytosis; nanoparticles; small-molecule inhibitor.
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