College of Chemical Engineering, Fuzhou University, Fuzhou, 350108, P. R. China.
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, P. R. China.
Adv Healthc Mater. 2022 Jun;11(11):e2102526. doi: 10.1002/adhm.202102526. Epub 2022 Feb 18.
Combinatorial photothermal and immunotherapy have demonstrated great potential to remove primary tumors, suppress metastases, and prevent tumor recurrence. However, this strategy still confronts patients with many limitations, such as complex components, sophisticated construction, and inadequate therapeutic efficacy. In this work, small molecules of porphyrin derivatives (PPor) which can self-assemble into monodispersed nanoparticles without supplement of any other ingredients or surfactants are developed. The formed PPor nanoparticles (PPor NPs) exhibit highly photothermal conversion efficiency of 70% and NIR-II luminous abilities originate from the strong intramolecular charge transfer (ICT) effect of D-A structure under 808 nm laser irradiation, thus achieving NIR-II fluorescence imaging guided photothermal therapy (PTT) against primary tumors with a high cure rate. More importantly, tumor-associated antigens (TAAs), together with damage-associated molecular patterns (DAMPs) released from PTT-treated cancer cells, are proved to elicit immune responses to some degree. After combination with programmed cell death-1 (PD-1) antibodies, a robust systematic antitumor immunity is generated to restrain both primary and abscopal tumors growth, prolong survival, and prevent pulmonary metastasis on an aggressive 4T1 murine breast tumor model. Thus, this study provides a promising therapeutic paradigm with porphyrin derivatives nano-assembly as phototheranostic agents for the treatment of aggressive tumors with high efficiency.
组合光热免疫疗法在消除原发性肿瘤、抑制转移和预防肿瘤复发方面显示出巨大的潜力。然而，这种策略仍然给患者带来了许多限制，如复杂的组成、复杂的构建和不足的治疗效果。在这项工作中，开发了卟啉衍生物（PPor）的小分子，这些小分子可以自组装成单分散的纳米颗粒，而不需要补充任何其他成分或表面活性剂。形成的 PPor 纳米颗粒（PPor NPs）表现出高达 70%的高光热转换效率和近红外二区（NIR-II）发光能力，这源于 D-A 结构在 808nm 激光照射下的强分子内电荷转移（ICT）效应，从而实现了 NIR-II 荧光成像引导的光热治疗（PTT），对原发性肿瘤有很高的治愈率。更重要的是，肿瘤相关抗原（TAAs）以及从 PTT 处理的癌细胞中释放的损伤相关分子模式（DAMPs），被证明在某种程度上引发了免疫反应。与程序性细胞死亡-1（PD-1）抗体结合后，会产生强大的系统抗肿瘤免疫，抑制原发性和远处肿瘤的生长，延长生存时间，并防止在侵袭性 4T1 小鼠乳腺癌模型中发生肺转移。因此，这项研究提供了一种有前途的治疗范例，卟啉衍生物纳米组装作为光热治疗剂，可高效治疗侵袭性肿瘤。
