Objective:Radical therapies are associated with significant morbidity in patients with localized prostate cancer (PCa). While advances in nuclear magnetic resonance techniques have enabled the development of focal ablation procedures that can selectively destroy tumors, preserve the gland and surrounding structures, and minimize side effects, existing vascular-targeted photodynamic therapy (VTP) and nanodrug therapies often face limitations, such as recurrence and insufficient drug concentration at the tumor site. This study investigated a novel approach that combines VTP with systemic treatment using drug-loaded nanoparticles in a murine model, demonstrating substantial advancements beyond current monotherapies.Methods:SCID (severe combined immunodeficiency) mice were engrafted with androgen-sensitive prostate tumor cells (LNCaP-AR) and treated with a combination of VTP and two different drugs linked to fucoidan nanoparticles (Enzalutamide and Paclitaxel). Experiments were performed using different cohorts: the evaluation of oncological effect, the administration time and concentration of systemic therapy, a comparison of efficacy between VTP and radiotherapy, and the induction of the abscopal effect in untreated synchronous tumors.Results:The groups that received combination therapy showed better tumor control. After eight weeks, the recurrence-free survival rates were 87.5%, 62.5%, and 50% in the VTP + N-PAC, VTP + N-ENZ, and VTP monotherapy groups, respectively (p< 0.05). There was a significant difference in the intra-tumoral concentration of nanodrugs between the groups with combined treatment and monotherapy. After two weeks, the monotherapy groups showed almost total elimination of the drugs, whereas in the combined therapy groups, this concentration remained high, starting to decrease after three weeks (p< 0.05). Treatment with nanodrugs associated with VTP showed superior oncological benefits compared to radiotherapy alone or in combination with other therapies. The abscopal effect on synchronous tumors was not demonstrated with VTP alone or in combination with nanodrugs.Conclusions: Combining vascular photodynamic therapy with nanodrugs was highly effective in treating a prostate tumor model, leading to increased survival and a reduced risk of tumor recurrence. This approach significantly advances beyond existing VTP and nanodrug therapies by improving tumor control, ensuring sustained intra-tumoral drug concentration, and yielding superior oncological outcomes. Our results suggest that this therapy is a potential treatment option for prostate tumors treated with VTP in future clinical trials.
目的：根治性疗法在局限性前列腺癌（PCa）患者中常伴随显著的并发症。尽管核磁共振技术的进步促进了局部消融术的发展，能够选择性破坏肿瘤、保留腺体及周围结构并减少副作用，但现有的血管靶向光动力疗法（VTP）和纳米药物疗法常面临复发及肿瘤部位药物浓度不足等局限。本研究在小鼠模型中探索了一种将VTP与载药纳米颗粒全身治疗相结合的新策略，其疗效显著超越了现有单一疗法。 方法：将雄激素敏感性前列腺肿瘤细胞（LNCaP-AR）移植至重症联合免疫缺陷（SCID）小鼠体内，采用VTP联合两种与岩藻聚糖纳米颗粒偶联的药物（恩杂鲁胺与紫杉醇）进行治疗。实验设置不同组别：评估肿瘤学疗效、全身治疗的给药时间与浓度、比较VTP与放疗的疗效，以及探究对未处理的同步肿瘤的远端效应。 结果：联合治疗组显示出更好的肿瘤控制效果。治疗八周后，VTP+N-PAC组、VTP+N-ENZ组和VTP单药组的无复发生存率分别为87.5%、62.5%和50%（p<0.05）。联合治疗组与单药组间纳米药物的瘤内浓度存在显著差异。治疗两周后，单药组药物几乎完全清除，而联合治疗组药物浓度仍维持较高水平，直至三周后才开始下降（p<0.05）。与单纯放疗或联合其他疗法相比，VTP联合纳米药物治疗展现出更优的肿瘤学获益。单独VTP或联合纳米药物治疗均未显示出对同步肿瘤的远端效应。 结论：血管光动力疗法联合纳米药物治疗在前列腺肿瘤模型中效果显著，可提高生存率并降低肿瘤复发风险。该方法通过改善肿瘤控制、维持持续的瘤内药物浓度及获得更优的肿瘤学结局，显著超越了现有VTP及纳米药物疗法。我们的研究结果表明，该疗法有望成为未来临床试验中VTP治疗前列腺肿瘤的潜在选择。
肿瘤(癌症)患者之家