A Glutathione (GSH)-Responsive Near-Infrared (NIR) Theranostic Prodrug for Cancer Therapy and Imaging

Abstract

To reduce the side effects of chemotherapy, nontoxic prodrugs activated by the tumor microenvironment are urgently required for use in cancer treatment. In this work, we developed prodrug 4 for tumor-targeting treatment and imaging of the anticancer drug release in vivo. Taking advantage of the high glutathione (GSH) concentration in cancer cells, the disulfide bond in prodrug 4 was cleaved, resulting in the release of an active anticancer drug and a near-infrared (NIR) fluorescence dye turn-on. Furthermore, contrast to the free anticancer drug, the prodrug exhibited higher cytotoxicity to hepatoma cells than that to normal HL-7702 cells. Thus, prodrug 4 is a promising platform for specific tumor-activatable drug delivery system, because of its favorable features of in situ and in vivo monitoring of the drug release and therapeutic efficacy.

In vivo imaging of leucine aminopeptidase activity in drug-induced liver injury and liver cancer via a near-infrared fluorescent probe

“…Stable hemicyanines with a hydroxyl group have recently been continually employed for preparing NIR probes, 8 but those with an amino group are seldom available except for some recent examples. 9 Here, we have successfully synthesized an amino hemicyanine (HCA) via two steps (Scheme S1†), and found that, similar to a hydroxyl hemicyanine, 8 amino substitution by leucine can efficiently quench the hemicyanine’s fluorescence, producing an extremely low background fluorescence, which is expected to afford high sensitivity.…”

Peptide‐Driven Targeted Drug‐Delivery System Comprising Turn‐On Near‐Infrared Fluorescent Xanthene–Cyanine Reporter for Real‐Time Monitoring of Drug Release

“…On the other hand, turn-onN IR fluorescent xanthene-cyanine dyes were recently designedf or spectrofluorometric and imaging-based detection of peroxynitrite, [13] fibroblasts, [14] aminopeptidase, [15,16] nitroxyl, [17] hydrogen polysulfide, [18] carboxylesterase, [19] hypochlorousa cid, [20] and glutathionine. [21,22] These dyes were also proposed for keloid diagnosis [23] and chemophotodynamic therapy. [24] However, the reported xanthene-cyanine dyesd id not contain reactive functionalities for binding to at argeting carrier and, until now,n one of them have been used for fluorescence TDD monitoring.…”

A Reaction‐Based Fluorescent Probe for Imaging of Native Hypochlorous Acid

“…[10][11][12][13][14] Synthetic small molecular fluorescent probesh ave been confirmed that were superior tools for trackingH OCl due to their high sensitivity,s electivity and easy manipulation. [15][16][17][18][19][20][21][22][23][24][25][26][27] Fluorescence imaging has been considered to be ah igh biocompatible imaging technique andh as been widely used ford etection of specific speciesa tt he cellular level for its noninvasive, realtime visualization, and high spatiala nd temporal resolution. [28][29][30][31][32][33] The conjunction of fluorescent probe and fluorescence imaging could provide us powerful tools for visualization of biologically relevant species.H ence, the fluorescent probesw ith high selectivity and sensitivity would able to trace the endogenousH OCl in living organisms.…”