Pt(IV)-conjugated drug-delivery system shows efficacy in glioblastoma therapy elsevierconnect harvardmed Glioblastoma BrainTumor DrugDelivery
By Nidhi Saha, BDSNov 18 2022Reviewed by Aimee Molineux A recent study published in the Journal of Controlled Release demonstrated a novel method for delivering anti-cancer drugs conjugated to modified cell-penetrating peptides across the blood-brain barrier in mice to treat glioblastoma .
However, cisplatin and other platinum-based drugs are not considered effective for treating GBM as they cannot penetrate the BBB. Due to similar reasons, current anti-cancer drugs pose little therapeutic benefits to GBM patients. It has been proposed that enhancing BBB penetrability can be of enormous value as it could facilitate greater intra-tumoral drug concentrations.
Previously, the researchers created M13 – a CPP Transportan 10 derivative, which was synthesized by adding a perfluoroaryl macrocycle to the latter. This change enables greater penetrability through the three-dimensional BBB spheroids in vitro and causes accumulation in the mouse brain in vivo. Pt -M13 facilitates platinum transport into the brain tissue of healthy mice, following conjugation to cis,cis,trans-[Pt 2Cl22], a Pt prodrug form of cisplatin.
A quantitative analysis of the platinum amounts in GBM-tumor-bearing mice was performed using ICP-MS to determine platinum's BBB-penetrating properties and biodistribution. Findings It was found that when compared to Pt alone, conjugation of the Pt prodrug to the M13 peptide significantly increased the cytotoxicity of Pt and decreased neurosphere growth in GBM cell lines. It was demonstrated in vitro that the drug-conjugated peptide killed GBM cells effectively.
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