Department of Chemical Biology and Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Anhui University of Technology, Ma'anshan 243032, People's Republic of China.
China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Nanotechnology. 2024 Nov 8;36(4). doi: 10.1088/1361-6528/ad8ce5.
The tumor microenvironment (TME) is characterized by low pH, hypoxia, and overexpression of glutathione (GSH). Owing to the complexity of tumor pathogenesis and the heterogeneity of the TME, achieving satisfactory efficacy with a single treatment method is difficult, which significantly impedes tumor treatment. In this study, composite nanoparticles of calcium-copper/alginate-hyaluronic acid (HA) (CaO-CuO@SA/HA NC) with pH and GSH responsiveness were prepared for the first time through a one-step synthesis using HA as a targeting ligand. Nanoparticles loaded with HOcan enhance the chemodynamic therapy effects. Simultaneously, Cucan generate oxygen in the TME and alleviate hypoxia in tumor tissue. Cuand HOundergo the Fenton reaction to produce cytotoxic hydroxyl radicals and Caions, which enhance the localization and clearance of nanoparticles in tumor cells. Additionally, HA and sodium alginate (SA) were utilized to improve the targeting and biocompatibility of the nanoparticles. Fourier transform infrared, x-ray diffraction, dynamic light scattering, SEM, transmission electron microscope, and other analytical methods were used to investigate their physical and chemical properties. The results indicate that the CaO-CuO@SA/HA NC prepared using a one-step method had a particle size of 220 nm, a narrow particle size distribution, and a uniform morphology. The hydrogen peroxide self-supplied nanodrug delivery system exhibited excellent pH-responsive release performance and glutathione-responsive •OH release ability while also reducing the level of reactive oxide species quenching.cell experiments, no obvious side effects on normal tissues were observed; however, the inhibition rate of malignant tumors HepG2 and DU145 exceeded 50%. The preparation of CaO-CuO@SA/HA NC nanoparticles, which can achieve both chemokinetic therapy and ion interference therapy, has demonstrated significant potential for clinical applications in cancer therapy.
肿瘤微环境（TME）的特点是 pH 值低、缺氧和谷胱甘肽（GSH）过表达。由于肿瘤发病机制的复杂性和 TME 的异质性，单一治疗方法难以达到令人满意的疗效，这显著阻碍了肿瘤的治疗。在这项研究中，首次通过一步合成法制备了具有 pH 和 GSH 响应性的钙铜/海藻酸钠-透明质酸（HA）复合纳米粒子（CaO-CuO@SA/HA NC），并使用 HA 作为靶向配体。负载 HOcan 的纳米粒子可以增强化学动力学治疗效果。同时，Cucan 在 TME 中产生氧气并缓解肿瘤组织中的缺氧。Cu 和 HO 通过芬顿反应产生细胞毒性羟基自由基和 Ca 离子，增强纳米粒子在肿瘤细胞中的定位和清除。此外，HA 和海藻酸钠（SA）被用于提高纳米粒子的靶向性和生物相容性。傅里叶变换红外、X 射线衍射、动态光散射、SEM、透射电子显微镜等分析方法被用于研究其物理和化学性质。结果表明，一步法制备的 CaO-CuO@SA/HA NC 的粒径为 220nm，粒径分布窄，形态均匀。过氧化氢自供纳米药物递送系统具有优异的 pH 响应释放性能和 GSH 响应•OH 释放能力，同时降低了活性氧化物物种的淬灭水平。细胞实验中，未观察到对正常组织的明显副作用；然而，恶性肿瘤 HepG2 和 DU145 的抑制率超过 50%。CaO-CuO@SA/HA NC 纳米粒子的制备能够实现化学动力学治疗和离子干扰治疗，在癌症治疗的临床应用中具有显著的潜力。
