Rational Design of a Hetero-multinuclear Gadolinium(III)–Copper(II) Complex: Integrating Magnetic Resonance Imaging, Photoacoustic Imaging, Mild Photothermal Therapy, Chemotherapy and Immunotherapy of Cancer,Journal of Medicinal Chemistry

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Rational Design of a Hetero-multinuclear Gadolinium(III)–Copper(II) Complex: Integrating Magnetic Resonance Imaging, Photoacoustic Imaging, Mild Photothermal Therapy, Chemotherapy and Immunotherapy of Cancer
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2024-08-14 , DOI: 10.1021/acs.jmedchem.4c01273
Xueyu Man ₁ , Wenjuan Li ₁ , Minghui Zhu ₁ , Shanhe Li ₁ , Gang Xu ₁ , Zhenlei Zhang ₁ , Hong Liang ₁ , Feng Yang ₁

Affiliation

For more accurate diagnosis and effective treatment of cancer, we proposed to develop a hetero-multinuclear metal complex based on the property of apoferritin (AFt) for targeting tumor theranostics by integrating dual-modality imaging diagnosis and multimodality therapy. To this end, we rational designed and synthesized a trinuclear Gd(III)–Cu(II) thiosemicarbazone complex (Gd-2Cu) and then constructed a Gd-2Cu@AFt nanoparticle (NP) delivery system. Gd-2Cu/Gd-2Cu@AFt NPs not only had significant T₁-weighted magnetic resonance imaging and photoacoustic imaging of the tumor but also effectively inhibited tumor growth through a combination of mild photothermal therapy, chemotherapy, and immunotherapy. Gd-2Cu@AFt NPs optimized the behavior of imaging diagnosis and therapy of Gd-2Cu, improved its targeting ability, and reduced the side effects in vivo. Besides, we revealed and clarified the anticancer mechanism of Gd-2Cu: interrupting energy metabolism of the tumor cell, inducing apoptosis of the tumor cell, and activating a systemic immune response by inducing immunogenic cell death of cancer cells.

中文翻译：

异质多核钆(III)-铜(II)络合物的合理设计：整合磁共振成像、光声成像、温和光热疗法、化疗和癌症免疫疗法

为了更准确地诊断和有效治疗癌症，我们提出基于脱铁铁蛋白（AFt）的特性开发一种异质多核金属配合物，通过整合双模态成像诊断和多模态治疗来靶向肿瘤治疗。为此，我们合理设计并合成了三核Gd(III)-Cu(II)缩氨基硫脲络合物( Gd-2Cu )，然后构建了Gd-2Cu @AFt纳米颗粒(NP)递送系统。 Gd-2Cu / Gd-2Cu @AFt NPs不仅对肿瘤具有显着的T ₁加权磁共振成像和光声成像，而且通过温和的光热疗法、化疗和免疫疗法的组合有效抑制肿瘤生长。 Gd-2Cu @AFt NPs优化了Gd-2Cu的影像诊断和治疗行为，提高了其靶向能力，降低了体内副作用。此外，我们还揭示并阐明了Gd-2Cu的抗癌机制：干扰肿瘤细胞的能量代谢，诱导肿瘤细胞凋亡，并通过诱导癌细胞的免疫原性细胞死亡来激活全身免疫反应。

更新日期：2024-08-14

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