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ZWZ-3，一种用于黑色素瘤成像和治疗的靶向线粒体的荧光探针。

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

作者信息

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

机构信息

National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China.

Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

出版信息

Front Pharmacol. 2022 Feb 23;13:829684. doi: 10.3389/fphar.2022.829684. eCollection 2022.

DOI:10.3389/fphar.2022.829684
PMID:35281928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8905922/
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 and . ZWZ-3 preferentially accumulated in melanoma cells 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. 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.

摘要

黑色素瘤耐药性和转移能力的增强导致患者预后不良。在此，我们设计并合成了一种新型的基于半花菁的荧光探针ZWZ-3，并研究了其在黑色素瘤成像和治疗方面的应用。ZWZ-3优先在黑色素瘤细胞中积累，这一过程依赖于有机阴离子转运多肽（OATP），该多肽将半花菁阳离子氮靶向线粒体。此外，我们研究了ZWZ-3在黑色素瘤中的作用及其分子机制。研究表明，ZWZ-3通过上调Bax并激活caspase-3、caspase-9和PARP，促进活性氧的产生并诱导线粒体介导的细胞凋亡。重要的是，ZWZ-3还通过上调LC-3II和Atg5并下调P62诱导自噬。它显著抑制了小鼠A375异种移植瘤的肿瘤生长，且无明显副作用。组织学和免疫组化分析表明，ZWZ-3诱导细胞凋亡并抑制肿瘤细胞增殖。因此，ZWZ-3是一种新型的诊疗试剂，可用于有效靶向、检测和治疗黑色素瘤。它还有助于监测疾病进展和对治疗的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8b/8905922/990aa379bb01/fphar-13-829684-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8b/8905922/59cb4ca67cef/fphar-13-829684-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8b/8905922/641c126d38ad/fphar-13-829684-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac8b/8905922/0020bb169d3b/fphar-13-829684-g003.jpg
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