一种光触发的自加速纳米平台用于多功能图像引导的综合抗癌免疫治疗。
A photo-triggered self-accelerated nanoplatform for multifunctional image-guided combination cancer immunotherapy.
发表日期:2023 Aug 25
作者:
Xiaoying Kang, Yuan Zhang, Jianwen Song, Lu Wang, Wen Li, Ji Qi, Ben Zhong Tang
来源:
Cell Death & Disease
摘要:
精确有效的图像引导免疫疗法在癌症治疗中具有巨大潜力。在本研究中,我们报道了一种自加速纳米平台,该平台结合了聚集诱导发光物质(AIEgen)和一种缺氧响应型化学药物,用于多功能图像引导联合免疫疗法。这种近红外AIEgen具有甲氧基取代,同时具备提高的荧光和光声亮度,具有强大的光吸收能力,以及增强的一型和二型光动力疗法(PDT)特性,通过增强的系间跃迁过程。通过将高性能的AIEgen与缺氧响应型紫杉醇(PTX)前药制成纳米粒子,并进一步伪造巨噬细胞细胞膜,构建了一种靶向肿瘤的治疗和诊断剂。荧光和光声成像的整合有助于敏感地描绘肿瘤部位,为肿瘤治疗提供准确的指导。光诱导的PDT效应可以消耗局部氧气,导致严重的缺氧,加速PTX药物的释放。结果表明,PDT和PTX化疗的组合诱导免疫原性癌细胞死亡,不仅能引发强烈的抗肿瘤免疫反应来抑制原发肿瘤的生长,而且还能抑制4T1肿瘤承载的雌性小鼠远处肿瘤的生长。在这里,我们报道了一种通过合理的分子设计来开发治疗和诊断剂的策略,用于促进抗肿瘤免疫疗法。© 2023. Springer Nature Limited.
Precise and efficient image-guided immunotherapy holds great promise for cancer treatment. Here, we report a self-accelerated nanoplatform combining an aggregation-induced emission luminogen (AIEgen) and a hypoxia-responsive prodrug for multifunctional image-guided combination immunotherapy. The near-infrared AIEgen with methoxy substitution simultaneously possesses boosted fluorescence and photoacoustic (PA) brightness for the strong light absorption ability, as well as amplified type I and type II photodynamic therapy (PDT) properties via enhanced intersystem crossing process. By formulating the high-performance AIEgen with a hypoxia-responsive paclitaxel (PTX) prodrug into nanoparticles, and further camouflaging with macrophage cell membrane, a tumor-targeting theranostic agent is built. The integration of fluorescence and PA imaging helps to delineate tumor site sensitively, providing accurate guidance for tumor treatment. The light-induced PDT effect could consume the local oxygen and lead to severer hypoxia, accelerating the release of PTX drug. As a result, the combination of PDT and PTX chemotherapy induces immunogenic cancer cell death, which could not only elicit strong antitumor immunity to suppress the primary tumor, but also inhibit the growth of distant tumor in 4T1 tumor-bearing female mice. Here, we report a strategy to develop theranostic agents via rational molecular design for boosting antitumor immunotherapy.© 2023. Springer Nature Limited.