Sonodynamic therapy (SDT) has emerged as a useful approach for tumor treatment. However, its widespread application is impeded by poor pharmacokinetics of existing sonosensitizers. Here we developed a metal-organic nanoplatform, wherein a small-molecule sonosensitizer (hematoporphyrin monomethyl ether, HMME) was ingeniously coordinated with zirconium, resulting in a multifunctional nanosonosensitizer termed Zr-HMME. Through post-synthetic modifications involving PEGylation and tumor-targeting peptide (F3) linkage, a nanoplatform capable of homing on melanoma was produced, which could elicit robust immune responses to suppress tumor lung metastasis in the host organism. Importantly, after seamless incorporation of positron-emitting Zr into this nanosonosensitizer, positron emission tomography (PET) could be used to monitor its pharmacokinetics. PET imaging studies revealed that this nanoplatform exhibited potent tumor accumulation and strong stability. Using intrinsic fluorescence from HMME, a dual-modal diagnostic capability (fluorescence and PET) was confirmed for this nanosonosensitizer. In addition, the mechanisms of how this nanoplatform interacted with immune system were also investigated. The collective data proved that the coordination structure between small-molecule drug cargos and metals may enhance the functions of each other while mitigating their weaknesses. This straightforward approach can expand the potential applications of suitable drug molecules.

中文翻译：

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正电子发射断层扫描引导多功能锆血卟啉纳米声敏剂协同治疗黑色素瘤


声动力疗法（SDT）已成为一种有效的肿瘤治疗方法。然而，现有声敏剂的药代动力学较差，阻碍了其广泛应用。在这里，我们开发了一种金属有机纳米平台，其中小分子声敏剂（血卟啉单甲醚，HMME）与锆巧妙地配位，产生了一种称为Zr-HMME的多功能纳米声敏剂。通过涉及聚乙二醇化和肿瘤靶向肽（F3）连接的合成后修饰，产生了能够靶向黑色素瘤的纳米平台，它可以引发强大的免疫反应来抑制宿主生物体中的肿瘤肺转移。重要的是，将正电子发射锆无缝融入这种纳米声敏剂后，正电子发射断层扫描（PET）可用于监测其药代动力学。 PET成像研究表明，该纳米平台表现出强大的肿瘤积累能力和很强的稳定性。利用 HMME 的固有荧光，证实了这种纳米声敏剂的双模式诊断能力（荧光和 PET）。此外，还研究了该纳米平台如何与免疫系统相互作用的机制。集体数据证明，小分子药物货物和金属之间的配位结构可以增强彼此的功能，同时减轻各自的弱点。这种简单的方法可以扩展合适药物分子的潜在应用。