Abstract
Glioblastoma multiforme (GBM) is a fatal brain cancer that has a dismal prognosis because of the blood-brain barrier (BBB) and the invasiveness of the tumors that make them difficult to treat. Chlorotoxin (ClTx) is a 36-amino acid peptide of scorpion Leiurus quinquestriatus venom that has become an extremely specific targeting agent of gliomas. Its action is binding to matrix metalloproteinase-2 (MMP-2), chloride channel ClC-3, and Annexin A2, which prevents tumor cell invasion, migration, and survival. This review identifies the multifunctional uses of chlorotoxin in the treatment of glioma. Chlorotoxin conjugates such as Tumor Paint (ClTx-Cy5.5) and Tozuleristide (BLZ-100) can be used in diagnostics to allow visualization of tumors and delineation of the margins during surgery. Chlorotoxin is a perfect targeting ligand to use in therapy, which improves the delivery of chemotherapeutic drugs (e.g., doxorubicin, temozolomide) across the BBB through functionalized nanocarriers such as liposomes and polymeric nanoparticles. This is a focused strategy that enhances antitumor activity and reduces systemic toxicity. Also, chlorotoxin has been demonstrated as a promising targeted radiotherapy (131I -TM -601) and a fusion conjugate with cytotoxic proteins (e.g., gelonin) to selectively kill tumor cells. The positive safety profile and tumor-specific targeting of chlorotoxin-based agents with the help of the initial clinical trials highlight their great potential to transform the diagnosis and treatment of glioma. Chlorotoxin is a paradigm shift to precision neuro-oncology, which is giving new hope to enhance patient outcomes.