Gan Zhaoyang, Liu Chang, Li Shaopeng, Ju Chengda, Huo Sixuan, Wang Jing, Lin Yulong
College of Pharmacy, Key Laboratory of Innovative Drug Development and Evaluation, Hebei Medical University, Shijiazhuang 050017, China.
Clinical College, Hebei Medical University, Shijiazhuang 050017, China.
Colloids Surf B Biointerfaces. 2025 Oct;254:114810. doi: 10.1016/j.colsurfb.2025.114810. Epub 2025 May 17.
To improve the treatment efficiency and targeted enrichment ability of tumors, in this study, a nanoplatform (FeCuSe@MONs-ART@HA) based iron copper selenide@mesoporous organosilica nanoparticles (FeCuSe@MONs) has been designed for synergistic chemotherapy (CT), photothermal therapy (PTT), and chemodynamic therapy (CDT). The photothermal performance and peroxidase-like activity of FeCuSe@MONs generated PTT-CDT synergistic therapy. The densely coated hyaluronic acid (HA) layers on the surface of FeCuSe@MONs not only improved the cancer-targeting efficiency but also prevented the nonspecific release of artesunate (ART). The high concentration of glutathione (GSH) and acid tumor microenvironment triggered the release of ART for chemotherapy, which simultaneously augmented the CDT efficiency of FeCuSe@MONs. Additionally, the glutathione peroxidase 4 (GPX4) levels significantly declined. MTT assay results indicated that FeCuSe@MONs-ART@HA demonstrates superior cytotoxic effects compared to FeCuSe@MONs@HA and ART alone. Furthermore, cells viability decreased to 18.75 % upon the application of an 808 nm laser. In vivo investigations further revealed that the FeCuSe@MONs-ART@HA + laser treatment group exhibited the highest rate of tumor growth inhibition, TGI% value reaching nearly 87.3 %, which was much higher than the 31.2 %, 45.6 % and 76.5 % in the groups of ART, FeCuSe@MONs@HA and FeCuSe@MONs@HA + laser. Owing to the synergistic effect, this nanoplatform significantly improved antitumor efficacy with minimal toxicity both in vitro and in vivo. These findings highlight such a CT-PTT-CDT synergistic drug delivery system showed great potential for treating tumors.
为提高肿瘤治疗效率和靶向富集能力，本研究设计了一种基于铁铜硒化物@介孔有机硅纳米粒子（FeCuSe@MONs）的纳米平台（FeCuSe@MONs-ART@HA），用于协同化疗（CT）、光热治疗（PTT）和化学动力学疗法（CDT）。FeCuSe@MONs的光热性能和类过氧化物酶活性产生了PTT-CDT协同治疗效果。FeCuSe@MONs表面密集包覆的透明质酸（HA）层不仅提高了癌症靶向效率，还防止了青蒿琥酯（ART）的非特异性释放。高浓度的谷胱甘肽（GSH）和酸性肿瘤微环境触发ART释放用于化疗，同时增强了FeCuSe@MONs的CDT效率。此外，谷胱甘肽过氧化物酶4（GPX4）水平显著下降。MTT检测结果表明，与单独的FeCuSe@MONs@HA和ART相比，FeCuSe@MONs-ART@HA具有更强的细胞毒性作用。此外，应用808 nm激光后细胞活力降至18.75%。体内研究进一步表明，FeCuSe@MONs-ART@HA +激光治疗组的肿瘤生长抑制率最高，TGI%值接近87.3%，远高于ART组、FeCuSe@MONs@HA组和FeCuSe@MONs@HA +激光组的31.2%、45.6%和76.5%。由于协同作用，该纳米平台在体外和体内均以最小的毒性显著提高了抗肿瘤疗效。这些发现突出了这种CT-PTT-CDT协同药物递送系统在治疗肿瘤方面具有巨大潜力。
