AUTHOR=Liu Zengjin , Wang Hailan , Sun Changzhen , He Yuanmin , Xia Tong , Wang Jianv , Xiong Xia , Zhang Qingbi , Yang Sijin , Liu Li 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.829684

DOI=10.3389/fphar.2022.829684

ISSN=1663-9812

ABSTRACT=The incidence of melanoma is increasing rapidly worldwide due to its increased drug resistance and high metastatic. Here, we designed and synthesized a novel hemicyanine-based fluorescent probe ZWZ-3 and investigated its apply for imaging and treating melanoma in vitro and in vivo. ZWZ-3 preferentially accumulated in the mitochondria of melanoma cells via a process that depended on the organic anion-transporting polypeptide (OATP). 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 based on upregulation of Bax and the activation of caspase-3, caspase-9, and PARP. Importantly, ZWZ-3 also induced autophagy by downregulating P62, while upregulating LC-3II, Atg5. It significantly suppressed tumor growth of A375 xenograft tumor model in mice, without obvious side effects. Histological and immunohistochemical analyses revealed that ZWZ-3 also induced apoptosis and inhibited tumor cell proliferation. Thus, ZWZ-3 represents a novel theranostic agent that can be used to effectively target, detect, and treat melanoma. it may also help to monitor disease progression and response to treatment.