Chlorotoxin is a polypeptide toxin isolated from the venom of the Israeli deathstalker scorpion[1-2]. Chlorotoxin selectively binds to the MMP-2 protein and chloride ion channels on the surface of glioma cells to inhibit tumor cell migration and invasion, while simultaneously blocking chloride ion currents to affect cellular volume changes. Chlorotoxin is applicable in the diagnosis, imaging, and therapeutic research of glioblastoma[3-4].
In vitro, Chlorotoxin (10nM-100μM) bound to superparamagnetic nanoparticles (NPC) and was applied to rat C6 glioma cells for 2 hours. Chlorotoxin significantly inhibited cell invasion and induced the internalization of lipid rafts containing MMP-2 and ion channels[5]. Chlorotoxin (0.05–5μM) was applied to human ER-positive breast cancer cells MCF-7, T47D, and ER-negative cells MDA-MB-231 for 12–72 hours. Chlorotoxin significantly inhibited cell proliferation, migration, and invasion in a concentration- and time-dependent manner, and downregulated the mRNA and protein expression levels of ERα, VASP, and MMP2 in the cells[6].
In vivo, Chlorotoxin (60μg/kg) was administered via intraperitoneal injection to tumor-bearing (SiHa cells) BALB/c nude mice, beginning when the tumor volume reached 50-100mm³ and repeated every 4 days. Chlorotoxin significantly enhanced the tumor-suppressive effect of cisplatin and downregulated the expression level of P-glycoprotein in tumor tissue[7]. Chlorotoxin (2μM; 10μL; single injection) was administered intrathecally to adult rats. Chlorotoxin significantly increased sciatic nerve injury and pain vulnerability in the rats[8].
References:
[1] Dardevet L, Rani D, Aziz TA, et al. Chlorotoxin: a helpful natural scorpion peptide to diagnose glioma and fight tumor invasion. Toxins (Basel). 2015 Mar 27;7(4):1079-101.
[2] Fu Y, An N, Li K, et al. Chlorotoxin-conjugated nanoparticles as potential glioma-targeted drugs. J Neurooncol. 2012 May;107(3):457-62.
[3] Cohen G, Burks SR, Frank JA. Chlorotoxin-A Multimodal Imaging Platform for Targeting Glioma Tumors. Toxins (Basel). 2018 Nov 26;10(12):496.
[4] Veiseh O, Gunn JW, Kievit FM, et al. Inhibition of tumor-cell invasion with chlorotoxin-bound superparamagnetic nanoparticles. Small. 2009 Feb;5(2):256-64.
[5] Tang J, Chen S, Deng Y, et al. MA104 cell line is permissive for human bocavirus 1 infection. J Virol. 2025 Feb 25;99(2):e0153924.
[6] Wang Y, Li K, Han S, et al. Chlorotoxin targets ERα/VASP signaling pathway to combat breast cancer. Cancer Med. 2019 Apr;8(4):1679-1693.
[7] Shen J, Zhang D, Zheng Q, et al. ClC-3 inhibition induces autophagy to reverse cisplatin resistance in cervical cancer via the Akt/mTOR pathway. Biochim Biophys Acta Mol Basis Dis. 2026 Jan;1872(1):168030.
[8] Zhang XL, Zhang JJ, Chen ZH, et al. Difference of pain vulnerability in adult and juvenile rodents: the role of SIRT1-mediated ClC-3 trafficking in sensory neurons. Pain. 2021 Jun 1;162(6):1882-1896.
Chlorotoxin是一种从以色列杀人蝎毒液中分离的多肽毒素[1-2]。Chlorotoxin可选择性结合胶质瘤细胞表面的MMP-2蛋白和氯离子通道来抑制肿瘤细胞迁移和侵袭，同时通过阻断氯离子电流以影响细胞体积变化。Chlorotoxin可用于胶质母细胞瘤的诊断、成像和治疗的相关研究[3-4]。
在体外，Chlorotoxin（10nM-100μM）结合超顺磁纳米颗粒(NPC)处理大鼠C6胶质瘤细胞2小时，Chlorotoxin显著抑制了细胞侵袭，并诱导MMP-2和离子通道的脂筏内化[5]。Chlorotoxin（0.05–5μM）处理人ER阳性乳腺癌细胞MCF-7、T47D细胞及ER阴性细胞MDA-MB-231，作用时间为12–72小时，Chlorotoxin以浓度和时间依赖性方式显著抑制细胞的增殖、迁移和侵袭，并下调细胞中ERα、VASP和MMP2的mRNA及蛋白表达水平[6]。
在体内，Chlorotoxin（60μg/kg）腹腔注射处理荷瘤（SiHa细胞）BALB/c裸鼠（自肿瘤体积达到50-100mm³后开始，每4天注射一次），Chlorotoxin显著增强顺铂的抑瘤效果，并下调肿瘤组织中P糖蛋白的表达水平[7]。Chlorotoxin（2μM；10μL；单次注射）经鞘内注射处理成年大鼠，Chlorotoxin显著增加了大鼠的坐骨神经损伤和疼痛易感性[8]。