Hypoxia-targeted cupric-tirapazamine liposomes potentiate radiotherapy in prostate cancer spheroids

In this study, novel cupric-tirapazamine [Cu(TPZ)2]-liposomes were developed as an effective hypoxia-targeted therapeutic, which potentiated radiotherapy in a three dimensional (3D) prostate cancer (PCa) model. To overcome the low water solubility of Cu(TPZ)2, remote loading method was to efficiently load lipophilic complex into different liposomal formulations. The effect pH, temperature, PEGylation, lipid composition, liposome size, lipid: ratio on properties, and drug evaluated. highest efficiency obtained at neutral independent composition incubation time. addition, enhanced achieved upon decreasing lipid:complex molar with minimal effects liposomes’ morphology. Interestingly, vitro potency liposomes easily manipulated by changing composition. hydrophilic nature our formulations improved complex’s solubility, leading cellular uptake toxicity, both PCa monolayers tumour spheroids. Moreover, Cu(TPZ)2-loaded combined radiation, showed significant reduction spheroids growth rate, compared free or radiation alone, could potentiate patients localised advanced PCa.