Center for Translational Medicine Research, Shanxi Medical University, Taiyuan, 030001, China.
College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan, 030024, China.
Small. 2021 Mar;17(10):e2006508. doi: 10.1002/smll.202006508. Epub 2021 Feb 11.
Multi-modality cancer diagnosis techniques based on the second near-infrared window fluorescence (NIR-II FL, 1000-1700 nm) imaging have become the focus of research attention. For such multimodality probes, how to take advantage of the tumor microenvironments (TME) characteristics to better image diseases and combine efficient therapeutics to achieve theranostics is still a big challenge. Herein, a novel TME-activated nanosystem (FMSN-MnO -BCQ) employing degradable silica-based nanoplatform is designed, adjusting the ratio of intratumoral hydrogen peroxide (H O )/glutathione (GSH) for magnetic resonance imaging (MRI)/NIR-II FL imaging and self-reinforcing chemodynamic therapy (CDT). Innovative bovine serum albumin (BSA)-modified fusiform-like mesoporous silica nanoparticles (FMSN) is fabricated as a carrier for NIR-II small molecule (CQ4T) and MRI reporter MnO . Remarkably, the BSA modification helped to achieve the dual-functions of high biocompatibility and enhance NIR-II fluorescence. The FMSN-MnO -BCQ with FMSN framework featuring a stepwise degradability in tumor interior released MnO and BCQ nanoparticles. Through the specific degradation of MnO by the TME, the produced Mn ions are effectively exerted Fenton-like activity to generate hydroxyl radical (•OH) from endogenous H O to eradicate tumor cells. More importantly, the GSH depletion due to the synergistic effect of tetrasulfide bond and MnO in turn induced the oxidative cytotoxicity for self-reinforcing CDT.
基于近红外二区荧光(NIR-II FL,1000-1700nm)成像的多模态癌症诊断技术已成为研究热点。对于这种多模态探针,如何利用肿瘤微环境(TME)的特点更好地对疾病进行成像,并结合有效的治疗方法实现治疗诊断一体化仍然是一个巨大的挑战。在此,设计了一种新型的 TME 激活纳米系统(FMSN-MnO -BCQ),采用可降解的硅基纳米平台,通过调节肿瘤内过氧化氢(H 2 O 2 )/谷胱甘肽(GSH)的比例,实现磁共振成像(MRI)/近红外二区荧光成像和自强化化学动力学治疗(CDT)。创新性地制备了牛血清白蛋白(BSA)修饰的梭形介孔硅纳米粒子(FMSN)作为 NIR-II 小分子(CQ4T)和 MRI 报告分子 MnO 的载体。值得注意的是,BSA 修饰有助于实现高生物相容性和增强 NIR-II 荧光的双重功能。FMSN-MnO -BCQ 以具有逐步降解性的 FMSN 骨架为特征,在肿瘤内部释放出 MnO 和 BCQ 纳米颗粒。通过 TME 对 MnO 的特异性降解,产生的 Mn 离子有效地发挥芬顿样活性,从内源性 H 2 O 产生羟基自由基(•OH)来消灭肿瘤细胞。更重要的是,由于四硫键和 MnO 的协同作用导致 GSH 耗竭,从而诱导自强化 CDT 的氧化细胞毒性。