■我们的研究旨在开发用于癌症治疗和实时荧光成像的双模态有机纳米试剂,然后对小鼠模型进行临床前评估。将近红外分子成像与纳米技术相结合,我们的目标是通过提供更有效和侵入性较小的方法来改善早期皮肤黑色素瘤的结局.这种方法有可能增强黑色素瘤患者的光热治疗(PTT)和前哨淋巴结活检(SLNB)程序。
■NIR-797-异硫氰酸酯封装在聚(D,L-丙交酯-共-乙交酯)酸(PLGA)纳米颗粒(NP)使用两步方案,接下来是彻底的表征,包括评估装载效率,荧光稳定性,和光热转换。在黑色素瘤细胞上进行了体外生物相容性和细胞摄取测试,而PTT测定,实时热监测,在用808nm激光照射下对荷瘤小鼠进行体内。最后,离体荧光显微镜,组织病理学测定,进行TEM成像。
■我们的PLGANP,直径为270纳米,负电荷,和60%的NIR-797装载效率,表现出优异的稳定性和荧光性能,以及高效的光热转换。体外研究证实了它们的生物相容性和细胞内化。体内实验证明了它们作为光热剂的功效,诱导温度高达43.8°C的轻度高温。肿瘤组织的离体显微镜检查证实了持续的NIR荧光和NP的均匀分布。组织病理学和TEM检测显示早期细胞凋亡,免疫细胞反应,超微结构损伤,和由NP处理和照射联合产生的细胞内物质碎片。此外,辐射区域边缘的TEM分析显示细胞损伤减弱,突出了我们靶向治疗方法的精确性和有效性。
■专门为双模态NIR功能量身定制,我们的NP为癌症PTT和实时荧光监测提供了一种新的方法,为临床翻译提供了一条有希望的途径。
UNASSIGNED: Our study seeks to develop dual-modal organic-nanoagents for cancer therapy and real-time fluorescence imaging, followed by their pre-clinical evaluation on a murine model. Integrating NIR molecular imaging with nanotechnology, our aim is to improve outcomes for early-stage cutaneous melanoma by offering more effective and less invasive methods. This approach has the potential to enhance both photothermal therapy (PTT) and Sentinel Lymph Node Biopsy (SLNB) procedures for melanoma patients.
UNASSIGNED: NIR-797-isothiocyanate was encapsulated in poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (NPs) using a two-step protocol, followed by thorough characterization, including assessing loading efficiency, fluorescence stability, and photothermal conversion. Biocompatibility and cellular uptake were tested in vitro on melanoma cells, while PTT assay, with real-time thermal monitoring, was performed in vivo on tumor-bearing mice under irradiation with an 808 nm laser. Finally, ex vivo fluorescence microscopy, histopathological assay, and TEM imaging were performed.
UNASSIGNED: Our PLGA NPs, with a diameter of 270 nm, negative charge, and 60% NIR-797 loading efficiency, demonstrated excellent stability and fluorescence properties, as well as efficient light-to-heat conversion. In vitro studies confirmed their biocompatibility and cellular internalization. In vivo experiments demonstrated their efficacy as photothermal agents, inducing mild hyperthermia with temperatures reaching up to 43.8 °C. Ex vivo microscopy of tumor tissue confirmed persistent NIR fluorescence and uniform distribution of the NPs. Histopathological and TEM assays revealed early apoptosis, immune cell response, ultrastructural damage, and intracellular material debris resulting from combined NP treatment and irradiation. Additionally, TEM analyses of irradiated zone margins showed attenuated cellular damage, highlighting the precision and effectiveness of our targeted treatment approach.
UNASSIGNED: Specifically tailored for dual-modal NIR functionality, our NPs offer a novel approach in cancer PTT and real-time fluorescence monitoring, signaling a promising avenue toward clinical translation.