State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China; Northwest Institute for Non-ferrous Metal Research, Xi'an 710016, China.
State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
J Colloid Interface Sci. 2022 Dec 15;628(Pt B):79-94. doi: 10.1016/j.jcis.2022.08.024. Epub 2022 Aug 8.
Hydrogel-based drug delivery holds great promise in topical tumor treatment. However, the simple construction of multifunctional therapeutic hydrogels under physiological conditions is still a huge challenge. Herein, for the first time, a multifunctional hyaluronan/MnO nanocomposite (HHM) hydrogel with injectable and self-healing capabilities was constructed under physiological conditions through innovative in situ mineralization-triggered Mn-hydrazide coordination crosslinking. The hydrogel formed from Mn and hydrazided hyaluronan under optimized conditions exhibited a high elastic modulus >1 kPa, injectability, self-healing function, stimuli-responsiveness and catalase-like activity. In vitro and in vivo biological experiments demonstrated that our HHM hydrogel could not only efficiently relieve hypoxia by in situ catalytic decomposition of endogenous HO into O but also achieve synergistic photodynamic/photothermal therapy of 4T1 breast cancer in a mouse tumor model. This study presented a novel mineralization-driven metal-hydrazide coordination crosslinking approach and developed a multifunctional therapeutic platform for O-enhanced efficient topical dual-phototherapy of breast cancer.
水凝胶载药在局部肿瘤治疗中具有广阔的应用前景。然而，在生理条件下构建多功能治疗性水凝胶仍然是一个巨大的挑战。在此，我们首次通过创新的原位矿化触发 Mn-酰腙配位交联，在生理条件下构建了具有注射和自修复能力的多功能透明质酸/MnO 纳米复合材料（HHM）水凝胶。在优化条件下，Mn 与酰腙化透明质酸形成的水凝胶具有较高的弹性模量（>1kPa）、可注射性、自修复功能、刺激响应性和类过氧化氢酶活性。体外和体内生物学实验表明，我们的 HHM 水凝胶不仅可以通过原位催化分解内源性 H2O2 产生的 O2 有效缓解缺氧，还可以在小鼠肿瘤模型中实现 4T1 乳腺癌的协同光动力/光热治疗。本研究提出了一种新的矿化驱动的金属酰腙配位交联方法，并开发了一种多功能治疗平台，用于 O2 增强的乳腺癌高效局部双重光疗。
