Highly-Efficient Gallium-Interference Tumor Therapy Mediated by Gallium-Enriched Prussian Blue Nanomedicine,ACS Nano

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Highly-Efficient Gallium-Interference Tumor Therapy Mediated by Gallium-Enriched Prussian Blue Nanomedicine
ACS Nano ( IF 15.8 ) Pub Date : 2024-01-10 , DOI: 10.1021/acsnano.3c10994
Junlie Yao _{1,

2} , Yue Qiu ₁ , Jie Xing ₁ , Zihou Li ₁ , Aoran Zhang _{1,

3} , Kewei Tu ₁ , Minjie Peng _{1,

3} , Xiaoxia Wu ₁ , Fang Yang _{1,

3,

4,

5} , Aiguo Wu _{1,

3,

4,

5}

Affiliation

Prussian blue (PB)-based nanomedicines constructed from metal ion coordination remain restricted due to their limited therapeutic properties, and their manifold evaluation complexity still needs to be unraveled. Owing to the high similarities of its ionic form to iron (Fe) and the resulting cellular homeostasis disruption performance, physiologically unstable and low-toxicity gallium (Ga) has garnered considerable attention clinically as an anti-carcinogen. Herein, Ga-based nanoparticles (NPs) with diverse Ga contents are fabricated in one step using PB with abundant Fe sites as a substrate for Ga substitution, which aims to overcome the deficiencies of both and develop an effective nanomedicine. A systematic comparison of their physicochemical properties effectively reveals the saturated Ga introduction state during the synthesis process, further identifying the most Ga-enriched PB NPs with a substitution content of >50% as a nanomedicine for subsequent exploration. It is verified that the Ga interference mechanisms mediated by the most Ga-enriched PB NPs are implicated in metabolic disorders, ionic homeostasis disruption, cellular structure dysfunction, apoptosis, autophagy, and target activation of the mammalian target of the rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) pathways. This study provides significant guidance on exploiting clinically approved agents for Ga interference and lays the foundation for the next generation of PB-based theranostic agents.

中文翻译：

富镓普鲁士蓝纳米药物介导的高效镓干扰肿瘤治疗

由金属离子配位构建的普鲁士蓝（PB）纳米药物由于其有限的治疗特性而仍然受到限制，并且其多方面评估的复杂性仍然需要阐明。由于其离子形式与铁（Fe）的高度相似性以及由此产生的细胞稳态破坏性能，生理不稳定且低毒性的镓（Ga）作为抗癌剂在临床上引起了相当大的关注。在此，利用具有丰富Fe位点的PB作为Ga取代的基质，一步制备了具有不同Ga含量的Ga基纳米颗粒（NPs），旨在克服两者的缺陷并开发一种有效的纳米药物。对其物理化学性质的系统比较有效地揭示了合成过程中饱和Ga的引入状态，进一步确定了取代含量>50%的最富Ga的PB NPs作为纳米药物，以供后续探索。经证实，大多数富含 Ga 的 PB NP 介导的 Ga 干扰机制与代谢紊乱、离子稳态破坏、细胞结构功能障碍、细胞凋亡、自噬以及雷帕霉素 (mTOR) 和有丝分裂原的哺乳动物靶点的靶点激活有关。 -激活蛋白激酶（MAPK）途径。这项研究为利用临床批准的 Ga 干扰药物提供了重要指导，并为下一代基于 PB 的治疗诊断药物奠定了基础。

更新日期：2024-01-10

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