Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Int J Nanomedicine. 2021 Apr 12;16:2775-2787. doi: 10.2147/IJN.S301552. eCollection 2021.
With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men's health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. This study was designed to develop dual-functional nanoparticles (NPs) which combined photothermal therapy (PTT) with immunotherapy and determine the anti-tumor efficacy for PCa treatment.
By a double emulsion technique, the drug nanocarrier, poly(lactic-co-glycolic acid) or PLGA, was applied for co-loading of a fluorescent dye, indocyanine green (ICG) and a toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) to synthesize PLGA-ICG-R848 NPs. Next, we determined their characteristic features and evaluated whether they inhibited the cell viability in multiple PCa cell lines. After treatment with PLGA-ICG-R848, the maturation markers of bone marrow-derived dendritic cells (BMDCs) were detected by flow cytometry. By establishing a subcutaneous xenograft model of mouse PCa, we explored both the anti-tumor effect and immune response following the NPs-based laser ablation.
With a mean diameter of 157.7 nm, PLGA-ICG-R848 exhibited no cytotoxic effect in PCa cells, but they significantly decreased RM9 cell viability to (3.9±1.0)% after laser irradiation. Moreover, PLGA-ICG-R848 promoted BMDCs maturation with the significantly elevated proportions of CD11c+CD86+ and CD11c+CD80+ cells. Following PLGA-ICG-R848-based laser ablation in vivo, the decreased bioluminescent signals indicated a significant inhibition of PCa growth, while the ratio of splenic natural killer (NK) cells in PLGA-ICG-R848 was (3.96±1.88)% compared with (0.99±0.10)% in PBS group, revealing the enhanced immune response against PCa.
The dual-functional PLGA-ICG-R848 NPs under laser irradiation exhibit the anti-tumor efficacy for PCa treatment by combining PTT with immunotherapy.
随着筛查技术的进步，越来越多的低危或中危前列腺癌（PCa）病例出现，这仍然对男性健康构成严重威胁。为了获得更好的疗效，人们越来越关注免疫疗法和局灶性治疗等新兴治疗方法的发展。然而，很少有研究提供关于是否以及如何将这些方法联合用于治疗 PCa 的指导。本研究旨在开发一种双重功能纳米颗粒（NPs），将光热疗法（PTT）与免疫疗法相结合，并确定其治疗 PCa 的抗肿瘤疗效。
通过双重乳液技术，将药物纳米载体聚（乳酸-共-乙醇酸）或 PLGA 用于共载荧光染料吲哚菁绿（ICG）和 Toll 样受体 7/8（TLR7/8）激动剂瑞喹莫德（R848），合成 PLGA-ICG-R848 NPs。接下来，我们确定了它们的特征，并评估了它们是否抑制了多种 PCa 细胞系的细胞活力。用 PLGA-ICG-R848 处理后，通过流式细胞术检测骨髓来源树突状细胞（BMDCs）的成熟标志物。通过建立小鼠 PCa 皮下移植瘤模型，我们探讨了基于 NPs 的激光消融后的抗肿瘤作用和免疫反应。
PLGA-ICG-R848 的平均直径为 157.7nm，在 PCa 细胞中无细胞毒性作用，但激光照射后可显著降低 RM9 细胞活力至（3.9±1.0）%。此外，PLGA-ICG-R848 可促进 BMDCs 成熟，CD11c+CD86+和 CD11c+CD80+细胞的比例显著升高。PLGA-ICG-R848 激光消融后，生物发光信号减少表明 PCa 生长受到显著抑制，而 PLGA-ICG-R848 组脾脏自然杀伤（NK）细胞比例为（3.96±1.88）%，PBS 组为（0.99±0.10）%，表明对 PCa 的免疫反应增强。
激光照射下的双重功能 PLGA-ICG-R848 NPs 通过将 PTT 与免疫疗法相结合，对 PCa 治疗具有抗肿瘤疗效。
Zotero 插件
