Engineering oxygen-deficient ZrO2-x nanoplatform as therapy-activated "immunogenic cell death (ICD)" inducer to synergize photothermal-augmented sonodynamic tumor elimination in NIR-II biological window
Engineering oxygen-deficient ZrO2-x nanoplatform as therapy-activated "immunogenic cell death (ICD)" inducer to synergize photothermal-augmented sonodynamic tumor elimination in NIR-II biological window
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DOI：
10.1016/j.biomaterials.2021.120787
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发表时间：
2021-04-02
期刊：
影响因子：
14
通讯作者：
Xue, Peng
中科院分区：
文献类型：
--
作者：
Jiao, Xiaodan;Sun, Lihong;Xue, Peng
纳米氧化锆作为一种两性半导体材料，已在光催化反应和压电传感器等领域得到了广泛的应用。然而，到目前为止，它在生物医学上的应用，特别是在抗肿瘤治疗中的应用，还很少被研究。在这里，首次合理设计和建立了表面聚乙二醇化和环-精氨酸-甘氨酸-天冬氨酸(CRGD)多肽功能化的氧化锆基纳米平台(ZrO2-x@PEG/cRGD，简称ZPR)，并将其用于治疗激活的免疫原性细胞死亡(ICD)？在NIR-II生物窗中促进光热增强声动力学肿瘤清除的诱导剂。所合成的ZPR纳米颗粒在900~1100 nm波长范围内具有很强的光吸收，使ZPR纳米颗粒在光热治疗(PTT)中的光热转换效率高达45.8%。此外，由于ZPR纳米颗粒表面存在丰富的氧缺陷，因此可以作为一类高性能的纳米声敏剂，其基础是在外部超声(US)作用下，电子(e？)/空穴(h+)对与能带之间的分离增强。更重要的是，声动力疗法(SDT)产生的细胞毒性活性氧(ROS)可以有效地诱导免疫原性细胞死亡(ICD)，这被认为是提高全身抗肿瘤免疫能力的重要手段，从而使治疗后肿瘤完全根除。体内移植瘤实验证明，在光声(PA)成像导航的辅助下，光热增强声动力疗法具有很高的治疗效果。值得注意的是，炎性细胞因子水平，包括I型干扰素、肿瘤坏死因子？(肿瘤坏死因子？)以及白细胞介素6(IL-6)在NIR-II/US照射后系统性升高，证实了免疫原性的提高。综上所述，这项研究为在不久的将来扩大氧化锆作为肿瘤治疗转化药的应用提供了有益的见解。
Nano-zirconia, as an amphoteric semiconductor, has been industrially exploited in photocatalytic reactions and as piezoelectric sensors. However, its biomedical applications, especially in antitumor therapeutics, have been seldom investigated to date. Here, oxygen-deficient zirconia (ZrO2-x)-based nanoplatform with surface PEGylation and cyclic-Arg-Gly-Asp (cRGD) peptide functionalization (ZrO2-x@PEG/cRGD, abbreviated as ZPR) was rationally designed and established for the first time, which was utilized as therapy-activated ?immunogenic cell death (ICD)? inducer to boost photothermal-augmented sonodynamic tumor elimination in NIR-II biological window. As-synthesized ZPR nanoparticles (NPs) exhibited intense optical absorbance in the wavelength range of 900?1100 nm, which endowed ZPR NPs with a photothermal conversion efficiency as high as 45.8% for photothermal therapy (PTT). Moreover, owing to the abundant surface oxygen defects, ZPR NPs can serve as a category of high-performance nano-sonosensitizer based on the strengthened separation of electron (e? )/hole (h+) pairs from the energy band under external ultrasound (US) activation. More importantly, cytotoxic reactive oxygen species (ROS) generated from sonodynamic therapy (SDT) can effectively induce immunogenic cell death (ICD), which is regarded to be significant to boost systemic anti-tumor immunity for rendering a complete tumor eradication post-treatment. In vivo experiments on tumor xenografts demonstrated the high therapeutic efficacy upon photothermal-augmented sonodynamic therapy, with the aid of photoacoustic (PA) imaging navigation. Remarkably, the level of inflammatory cytokines, including type I interferon (IFN), tumor necrosis factor ? (TNF?) as well as interleukin (IL-6) were systemically upgraded after NIR-II/US irradiation, verifying the promotion of immunogenicity. Taken together, this study delivers useful insights for extending the applications of zirconia as promising translational medicine for tumor theranostics in the near future.