Shaanxi Key Laboratory of Chemical Additives for Industry, College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China.
School of Pharmacy, Xi'an Medical University, Xi'an 710021, China.
J Colloid Interface Sci. 2023 May;637:399-407. doi: 10.1016/j.jcis.2023.01.110. Epub 2023 Jan 26.
The amplified oxidative stress strategy has been emerged as one promising method to enhance the chemodynamic therapy (CDT) efficacy due to the HO up-regulation and glutathione (GSH) down-regulation behavior in tumor cells. However, how to further achieve the satisfied CDT efficacy is still a big challenge. In this paper, the supramolecular nanovalves (SNs) with oxidative amplification agents cinnamaldehyde-(phenylboronic acid pinacol ester) conjugates (CA-BE) encapsulated inside were developed to accelerate and amplify the generation of ·OH and consumption of GSH while augmenting the CDT efficacy. SNs were obtained through ferrocene/Au modified mesoporous silica nanoparticles (MSN@Au-Fc) and active targeting β-cyclodextrin modified hyaluromic acid (HA-CD). After CD44 receptor-mediated cellular internalization, the CA-BE were released to elevate HO amount and consume GSH for the desired generation of higher cytotoxic hydroxyl radicals (·OH). Moreover, the NIR-activated MSN@Au-Fc can increase the temperature for the accelerated and amplified oxidative stress. As such, the therapeutic efficacy of our synthesized CA-BE and the accompanied hyperthermia were augmented toward synergistically inhibiting tumor growth.
由于肿瘤细胞中 HO 的上调和谷胱甘肽 (GSH) 的下调行为，放大氧化应激策略已成为增强化学动力学治疗 (CDT) 疗效的一种很有前途的方法。然而，如何进一步实现令人满意的 CDT 疗效仍然是一个巨大的挑战。本文开发了具有氧化放大剂肉桂醛-(苯硼酸频哪醇酯) 缀合物 (CA-BE) 封装在内的超分子纳米阀 (SNs)，以加速和放大·OH 的产生和 GSH 的消耗，同时增强 CDT 疗效。SNs 通过二茂铁/金修饰的介孔硅纳米粒子 (MSN@Au-Fc) 和主动靶向 β-环糊精修饰的透明质酸 (HA-CD) 获得。在 CD44 受体介导的细胞内化后，CA-BE 被释放以提高 HO 量并消耗 GSH，从而产生更高细胞毒性的羟基自由基 (·OH)。此外，NIR 激活的 MSN@Au-Fc 可以升高温度，以加速和放大氧化应激。因此，我们合成的 CA-BE 的治疗效果以及伴随的热疗协同抑制肿瘤生长的效果得到增强。
