Tumor microenvironment-responsive self-assembly of barium titanate nanoparticles with enhanced piezoelectric catalysis capabilities for efficient tumor therapy,Bioactive Materials

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Tumor microenvironment-responsive self-assembly of barium titanate nanoparticles with enhanced piezoelectric catalysis capabilities for efficient tumor therapy
Bioactive Materials ( IF 18.0 ) Pub Date : 2023-11-20 , DOI: 10.1016/j.bioactmat.2023.11.004
Zhuo Xiang ₁ , Lingling Xu _{2,

3,

4} , Yizhu Shan _{2,

3} , Xi Cui _{2,

3} , Bojing Shi _{2,

5} , Yuan Xi _{2,

6} , Panxing Ren _{2,

3} , Xuemei Zheng ₇ , Chaochao Zhao ₈ , Dan Luo _{2,

3} , Zhou Li _{1,

2,

3}

Affiliation

Center on Nanoenergy Research, School of Physical Science & Technology, Guangxi University, Nanning, 530004, China.
Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, China.
School of Nanoscience and Technology, University of Chinese Academy of Sciences, Beijing, 100049, China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, China.
School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China.
Beijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, School of Engineering Medicine, Beihang University, Beijing, 100191, China.
College of Chemistry and Chemical Engineering, Center on Nanoenergy Research, Guangxi University, Nanning, 530004, China.
Department of Biomedical Engineering, School of Medicine, Foshan University, Foshan, 528225, China.

Catalytic therapy based on piezoelectric nanoparticles has become one of the effective strategies to eliminate tumors. However, it is still a challenge to improve the tumor delivery efficiency of piezoelectric nanoparticles, so that they can penetrate normal tissues while specifically aggregating at tumor sites and subsequently generating large amounts of reactive oxygen species (ROS) to achieve precise and efficient tumor clearance. In the present study, we successfully fabricated tumor microenvironment-responsive assembled barium titanate nanoparticles (tma-BTO NPs): in the neutral pH environment of normal tissues, tma-BTO NPs were monodisperse and possessed the ability to cross the intercellular space; whereas, the acidic environment of the tumor triggered the self-assembly of tma-BTO NPs to form submicron-scale aggregates, and deposited in the tumor microenvironment. The self-assembled tma-BTO NPs not only caused mechanical damage to tumor cells; more interestingly, they also exhibited enhanced piezoelectric catalytic efficiency and produced more ROS than monodisperse nanoparticles under ultrasonic excitation, attributed to the mutual extrusion of neighboring particles within the confined space of the assembly. tma-BTO NPs exhibited differential cytotoxicity against tumor cells and normal cells, and the stronger piezoelectric catalysis and mechanical damage induced by the assemblies resulted in significant apoptosis of mouse breast cancer cells (4T1); while there was little damage to mouse embryo osteoblast precursor cells (MC3T3-E1) under the same treatment conditions. Animal experiments confirmed that peritumoral injection of tma-BTO NPs combined with ultrasound therapy can effectively inhibit tumor progression non-invasively. The tumor microenvironment-responsive self-assembly strategy opens up new perspectives for future precise piezoelectric-catalyzed tumor therapy.

中文翻译：

具有增强压电催化能力的钛酸钡纳米颗粒的肿瘤微环境响应自组装，用于高效肿瘤治疗

基于压电纳米粒子的催化治疗已成为消除肿瘤的有效策略之一。然而，如何提高压电纳米粒子的肿瘤递送效率，使其能够穿透正常组织，同时特异性聚集在肿瘤部位，随后产生大量的活性氧（ROS）以实现精确高效的肿瘤清除，仍然是一个挑战。在本研究中，我们成功制备了肿瘤微环境响应组装钛酸钡纳米颗粒（tma-BTO NPs）：在正常组织的中性 pH 环境中，tma-BTO NPs 是单分散的，具有穿过细胞间隙的能力;而肿瘤的酸性环境触发了 tma-BTO NPs 的自组装，形成亚微米级聚集体，并沉积在肿瘤微环境中。自组装的 tma-BTO NPs 不仅对肿瘤细胞造成机械损伤;更有趣的是，在超声激发下，它们还表现出增强的压电催化效率，并且比单分散纳米颗粒产生更多的 ROS，这归因于相邻颗粒在组件的有限空间内的相互挤压。tma-BTO NPs 对肿瘤细胞和正常细胞表现出不同的细胞毒性，并且组件诱导的更强的压电催化和机械损伤导致小鼠乳腺癌细胞显着凋亡（4T1）;而在相同的处理条件下，小鼠胚胎成骨细胞前体细胞（MC3T3-E1）损伤很小。动物实验证实，瘤周注射 tma-BTO NPs 联合超声治疗可有效无创抑制肿瘤进展。肿瘤微环境响应自组装策略为未来精准压电催化肿瘤治疗开辟了新的前景。

更新日期：2023-11-20

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