利用金属有机框架（MOF）的光动力疗法（PDT）已发展成为一种针对人体表面恶性肿瘤的有效治疗方法。为了达到更有效的PDT治疗效果，传统的方法一直是增加激光照射的强度，但这种方法很容易导致组织烧伤。在这项研究中，我们开发了一种新型纳米颗粒 F68-PKI@PCN224，旨在对甲状腺髓样癌 (MTC) 实现有效的 PDT，MTC 是一种罕见的甲状腺癌，起源于甲状腺滤泡旁细胞，治疗方法MTC 患者的前景仍然不能令人满意。 F68-PKI@PCN224 将 PDT 的抗肿瘤特性与哺乳动物雷帕霉素靶点 (mTOR) 抑制剂 PKI-587 (PKI) 相结合。 F68-PKI@PCN224 的肿瘤致敏、缓慢释放和 pH 响应特性通过一系列体外和体内实验/测定得到证明。 F68-PKI@PCN224实现了MTC肿瘤组织中PKI和TCPP的长期激活和缓慢释放。在产生PDT效应的过程中，F68-PKI@PCN224增强了肿瘤对PDT、直接激光照射MTC细胞或皮下肿瘤组织的敏感性。因此，与 TCPP 相比，低剂量光疗对 F68-PKI@PCN224 具有更高的抗肿瘤效果。这项研究揭示了 mTOR 抑制剂和 PDT 的肿瘤致敏作用之间的协同作用，并初步揭示了这些纳米颗粒的作用机制。版权所有 © 2024。由 Elsevier B.V. 出版。

Photodynamic therapy (PDT) utilizing metal-organic frameworks (MOFs) has developed as a new and efficacious treatment for malignant tumors located on the surface of the human body. In order to achieve more effective PDT treatment outcomes, the traditional method has been to increase the intensity of the laser irradiation, but this approach can easily lead to tissue burns. In this study, we developed a new type of nanoparticle, F68-PKI@PCN224, aims to achieve effective PDT upon medullary thyroid carcinoma (MTC) which is an uncommon form of thyroid cancer that originates in the parafollicular cells of the thyroid and the therapeutic outlook for patients with MTC remains unsatisfactory. F68-PKI@PCN224 combines the antitumor features of PDT with mammalian target of rapamycin (mTOR) inhibitor PKI-587 (PKI). The tumor sensitization, slow release, and pH response features of F68-PKI@PCN224 was demonstrated by a series of in vitro and in vivo experiments / assays. F68-PKI@PCN224 achieved the long-term activation and slow releasing of PKI and TCPP in MTC tumor tissues. During the process of generating PDT effects, F68-PKI@PCN224 enhanced the tumor's sensitivity to PDT, direct laser irradiation of MTC cells or subcutaneous tumor tissues. As a result, low-dose phototherapy achieves a higher anti-tumor effect upon F68-PKI@PCN224 compared with TCPP. This study reveals the synergistic effect between tumor sensitization by mTOR inhibitor and PDT and initially unveils the mechanism of action of these nanoparticles.Copyright © 2024. Published by Elsevier B.V.