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Ferrocene and glucose oxidase-installed multifunctional hydrogel reactors for local cancer therapy
Journal of Controlled Release ( IF 10.8 ) Pub Date : 2022-07-26 , DOI: 10.1016/j.jconrel.2022.07.017
Song Yi Lee 1 , JiHye Park 2 , Da In Jeong 2 , ChaeRim Hwang 2 , Junmin Lee 3 , KangJu Lee 4 , Han-Jun Kim 5 , Hyun-Jong Cho 2
Affiliation  

A hyaluronic acid (HA)-based one-pot hydrogel reactor with single syringe injection and immediate gelation was developed for starvation therapy (ST), chemodynamic therapy (CDT), ferroptosis, and photothermal therapy (PTT) against breast cancer. A rheologically tuned hydrogel network, composed of HA-phenylboronic acid (HP) and HA-dopamine (HD), was designed by introducing a boronate ester linkage (phenylboronic acid-dopamine interaction) and polydopamine bond (pH control). Ferrocene (Fc)-conjugated HP (Fc-HP) was synthesized to achieve ferroptosis, Fenton reaction-involved toxic hydroxyl radical (OH) generation, and photothermal ablation in cancer therapy. Glucose oxidase (GOx) was entrapped in the pH-modulated Fc-HP (Fc-HP°)/HD hydrogel network for converting intracellular glucose to H2O2 to enable its own supply. The GOx/Fc combination-installed hydrogel reactor system can provide sustained ST/CDT/PTT functions along with ferroptosis. Injection of Fc-HP°/HD/GOx hydrogel with single-syringe injectability, shear-thinning feature, and self-healing capability offered a slow biodegradation rate and high safety profiles. Peritumorally injected Fc-HP°/HD/GOx hydrogel also efficiently suppressed the growth of breast cancer based on multifunctional therapeutic approaches with reduced dosing frequency. Hyperthermia induced by near-infrared (NIR) laser absorption may amplify the therapeutic effects of free radicals. It is expected that this Fc-HP°/HD/GOx hydrogel system can be applied to local cancer therapy with high efficacy and safety profiles.



中文翻译:

安装二茂铁和葡萄糖氧化酶的多功能水凝胶反应器用于局部癌症治疗

开发了一种基于透明质酸 (HA) 的一锅水凝胶反应器,该反应器具有单注射器注射和立即凝胶化,用于针对乳腺癌的饥饿疗法 (ST)、化学动力学疗法 (CDT)、铁死亡和光热疗法 (PTT)。通过引入硼酸酯键(苯基硼酸-多巴胺相互作用)和聚多巴胺键(pH 控制)设计了由 HA-苯基硼酸 (HP) 和 HA-多巴胺 (HD) 组成的流变调节水凝胶网络。合成二茂铁 (Fc)-共轭 HP (Fc-HP) 以实现铁死亡、芬顿反应涉及的有毒羟基自由基 ( OH) 生成以及癌症治疗中的光热消融。葡萄糖氧化酶 (GOx) 被包裹在 pH 调节的 Fc-HP (Fc-HP°)/HD 水凝胶网络中,用于将细胞内葡萄糖转化为 H 2O 2启用自己的供应。安装 GOx/Fc 组合的水凝胶反应器系统可以提供持续的 ST/CDT/PTT 功能以及铁死亡。具有单注射器可注射性、剪切稀化特性和自愈能力的 Fc-HP°/HD/GOx 水凝胶注射提供了缓慢的生物降解率和高安全性。基于减少给药频率的多功能治疗方法,瘤周注射的 Fc-HP°/HD/GOx 水凝胶也有效地抑制了乳腺癌的生长。近红外 (NIR) 激光吸收引起的热疗可能会放大自由基的治疗效果。预计这种 Fc-HP°/HD/GOx 水凝胶系统可应用于局部癌症治疗,具有高效和安全性。

更新日期:2022-07-26
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