ZWZ-3, a Fluorescent Probe Targeting Mitochondria for Melanoma Imaging and Therapy

Abstract

The increased drug resistance and metastasis of melanoma resulted in poor prognosis of patients. Here, we designed and synthesized a novel hemicyanine-based fluorescent probe ZWZ-3, and investigated its application for melanoma imaging and treatment both in vitro and in vivo. ZWZ-3 preferentially accumulated in melanoma cells via a process that depended on the organic anion-transporting polypeptide (OATP), which targeted mitochondria on the hemicyanine cationic nitrogen. In addition, we investigated the effect and molecular mechanism of ZWZ-3 in melanoma. In vitro studies showed that ZWZ-3 promoted the generation of reactive oxygen species and induced mitochondrial-mediated cell apoptosis by upregulating Bax and activating caspase-3, caspase-9, and PARP. Importantly, ZWZ-3 also induced autophagy by upregulating LC-3II and Atg5 and downregulating P62. It significantly suppressed tumor growth of A375 xenograft tumor in mice without notable side effects. Histological and immunohistochemical analyses revealed that ZWZ-3 induced apoptosis and inhibited tumor cell proliferation. Thus, ZWZ-3 represents a novel theranostic agent that can be used to effectively targeting, detecting, and treating melanoma. It could also help monitoring disease progression and response to treatment.

A novel mitochondria‐targeting compound exerts therapeutic effects against melanoma by inducing mitochondria‐mediated apoptosis and autophagy in vitro and in vivo

“…After discarding the culture medium, MitoTracker Green (200 nM) was added and incubated for 45 min. Finally, images were taken using a fluorescence microscope 22 …”

“…Cell viability was detected using the MTT assay. 22 A375, B16, and 293T cells that underwent log-phase growth were inoculated into 96-well cell culture plates (1-5 Â 10 3 cells per well). After overnight incubation, the cells were exposed to various concentrations of SCZ0148 (20, 10, 5, 2.5, 1.25, and 0.625 μM) for different durations (24,48, and 72 h).…”

“…19 Anthocyanin cationic fluorophores tend to accumulate in mitochondria and are widely used in tumor imaging and treatment. [20][21][22][23] Therefore, modification of compounds based on the structure of cyanine is a potential method for obtaining mitochondria-targeting drugs.…”

Identification of an ergosterol derivative with anti-melanoma effect from the sponge-derived fungus Pestalotiopsis sp. XWS03F09

“…Tumor tissues fixed in formalin were subjected to hematoxylin and eosin (H&E) to detect whether there are any toxic and side effects on normal organs and immunohistochemistry analysis to detect anti-Ki67 and cleaved caspase-3 ( Liu et al, 2022 ).…”

Dextran Fluorescent Probes Containing Sulfadiazine and Rhodamine B Groups

“…However, since these probes are excreted from the body quickly and usually demonstrate no tumor-targeting biodistribution, they then possess significant restrictions for the imaging of tumors [ 9 , 10 , 11 ]. To find a potential solution to this, a tumor-targeting fluorescent probe is an ideal trend to achieve bioimaging with high sensitivity, resolution, and imaging-contrast enhancement, as well as suitable long duration and excretion time in vivo [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”