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Título

A NOVEL P-SELECTIN TARGET NANOPARTICLES CHEMOTHERAPY DELIVERY COMBINED WITH WST-11 VASCULAR TARGET PHOTODYNAMIC THERAPY (TOOKAD-VTP) TO IMPROVE LOCAL TUMOR CONTROL IN A PROSTATE CANCER MODEL

Introdução, Material, Método, Resultados, Discussão e Conclusões

INTRODUCTION AND OBJECTIVE: In a recent Phase III randomized trial, TOOKAD-VTP has showed great efficacy in low risk prostate cancer (PCa) patients. However, about 28% of these patients presented disease progression after 2 years. P-selectin, an inflammatory cell adhesion molecule has been described as a potential target for cancer drug delivery, as Fucoidan-encapsulated chemotherapy. We describe the local tumor control improvement after single dose of Fucoidan-encapsulated paclitaxel and enzalutamide nanoparticles combined with VTP ablation in a PCa model.
METHODS: 36 male SCID mice, injected with LNCap tumor cells, were arranged in 6 different groups: Control, Nano-Enzalutamide (ENZA), Nano-Paclitaxel, VTP, VTP + Nano-ENZA (VE) and VTP + Nano-Paclitaxel (VP). Nano-drugs were administrated single dose (ENZA=50mg/Kg and Paclitaxel=5mg/Kg), 24 hs before VTP. IVIS images were done at 5 different timepoints: a day after VTP and weekly until 4 weeks after VTP ablation. Tumors measurements and relapses records were done weekly until 8 weeks after VTP treatment.
RESULTS: After 8 weeks from VTP ablation, the relapse free survival rate was 87.5% (1/8 mouse relapsed), 62.5% (3/8 mice relapsed) and 50% (4/8 mice relapsed) in the VTP + Nano-Paclitaxel group (VP), VTP+ Nano-Enzalutamide group (VE) and VTP alone group, respectively (p<0.05- Figure 1). IVIS images comparison showed a significant difference in the concentration of the nanoparticles inside the tumor between VTP + Nano-drugs groups (VE and VP) and Nano-drugs alone groups (Figure2). One week after Nano-drugs administration, the mean of nanoparticles concentration in the VTP + Nano-drugs groups were the double compared to the Nano-drugs alone, showing a stronger affinity of the nanoparticles to the tumor site after ablation. Two weeks after, the Nano-drugs groups had almost no more signal at the tumor site (total clearance) whether in the VTP + nano-drugs groups, the concentration stayed high and started to droop only 3 weeks after nanoparticles administration (p<0.05), confirming the “drug trap” effect of VTP, already published by our lab.
CONCLUSION: P-selectin target nanoparticles chemotherapy combined with VTP ablation is a promising approach to improve local tumor control and decrease tumor relapses in a prostate cancer model. The concept of single dose combination and the high tumor-specific affinity seems to be effective and potentially decreases the risk of chemotherapy side effects.

Palavras Chave

VASCULAR TARGET PHOTODYNAMIC THERAPY, PROSTATE CANCER, NANOPARTICLES

Área

Câncer de Próstata Localizado