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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.
VASCULAR TARGET PHOTODYNAMIC THERAPY, PROSTATE CANCER, NANOPARTICLES
Câncer de Próstata Localizado
Memorial Sloan Kettering Cancer Center - - Estados Unidos
RICARDO ALVIM, Lucas Nogueira, HANAN BAKER, NATHAN WONG, KARAN NAGAR, JASMINE THOMAS, ANDREW TRACEY, kWANGHEE KIM, DANIEL HELLER, JONATHAN COLEMAN