Enhanced Sonodynamic Therapy for Deep Tumors Using a Self-Assembled Organoplatinum(II) Sonosensitizer.

IF 5.3 2区材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY

ACS Applied Nano Materials Pub Date : 2024-10-24 Epub Date: 2024-10-03 DOI:10.1021/acs.jmedchem.4c01671

Haobing Wang, Dan Li, Hanqiang Wang, Qingyan Ren, Yue Pan, Anyi Dao, Deliang Wang, Zhigang Wang, Pingyu Zhang, Huaiyi Huang

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Abstract

Despite the promising advances in photodynamic therapy (PDT), it remains challenging to target and treat deep-seated solid tumors effectively. Herein, we developed an organoplatinum(II) complex (Pt-TPE) with self-assembly properties for sonodynamic therapy (SDT). Pt-TPE forms a nanofiber network structure through Pt-Pt and π-π stacking interactions. Notably, under ultrasound (US), Pt-TPE demonstrates unique self-assembly-induced singlet oxygen (¹O₂) generation due to a significantly enhanced singlet-triplet intersystem crossing (ISC). This generation of ¹O₂ occurs exclusively in the self-assembled state of Pt-TPE. Additionally, Pt-TPE exhibits sono-cytotoxicity against cancer cells by impairing mitochondrial membrane potential (MMP), inhibiting glucose uptake, and aerobic glycolysis. Furthermore, US-activated Pt-TPE significantly inhibits deep solid tumors in mice, achieving remarkable therapeutic efficacy even at penetration depths greater than 10 cm. This study highlights the potential of self-assembled metal complexes to enhance the efficacy of SDT for treating deep tumors.

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利用自组装有机铂（II）声敏化剂增强深部肿瘤的声动力疗法

尽管光动力疗法（PDT）取得了令人鼓舞的进展，但有效靶向和治疗深部实体瘤仍是一项挑战。在此，我们开发了一种具有自组装特性的有机铂（II）复合物（Pt-TPE），用于声动力疗法（SDT）。Pt-TPE通过Pt-Pt和π-π堆叠相互作用形成纳米纤维网络结构。值得注意的是，在超声（US）条件下，由于单线-三线系统间交叉（ISC）显著增强，Pt-TPE 显示出独特的自组装诱导单线态氧（1O2）生成。这种 1O2 生成完全发生在 Pt-TPE 的自组装状态。此外，Pt-TPE 还能损害线粒体膜电位 (MMP)、抑制葡萄糖摄取和有氧糖酵解，从而对癌细胞产生声毒性。此外，US 激活的 Pt-TPE 还能显著抑制小鼠体内的深部实体瘤，即使穿透深度超过 10 厘米，也能取得显著疗效。这项研究凸显了自组装金属复合物在提高 SDT 治疗深部肿瘤疗效方面的潜力。

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来源期刊

ACS Applied Nano Materials Multiple-

CiteScore

8.30

自引率

3.40%

发文量

1601

期刊介绍： ACS Applied Nano Materials is an interdisciplinary journal publishing original research covering all aspects of engineering, chemistry, physics and biology relevant to applications of nanomaterials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important applications of nanomaterials.