研究动态
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一种多功能、高生物兼容性和双触发焦糖化纳米治疗系统,负载有Fe3O4和DOX,可通过联合化疗-光热疗法实现对三阴性乳腺癌的治疗,并实时进行磁共振成像监测。

A Multifunctional, Highly Biocompatible, and Double-Triggering Caramelized Nanotheranostic System Loaded with Fe3O4 and DOX for Combined Chemo-Photothermal Therapy and Real-Time Magnetic Resonance Imaging Monitoring of Triple Negative Breast Cancer.

发表日期:2023
作者: Fangqing Wang, Nianlu Li, Wenbo Wang, Long Ma, Yaru Sun, Hong Wang, Jinhua Zhan, Dexin Yu
来源: International Journal of Nanomedicine

摘要:

由于缺乏特定的分子靶点,目前针对三阴性乳腺癌(TNBC)的临床治疗策略仍然有限。近年来,一些针对恶性肿瘤治疗的纳米系统引起了相当多的关注。在本研究中,我们制备了加载阿霉素(DOX)和Fe3O4的焦糖化纳米球(CNSs),以实现联合治疗的协同作用和实时磁共振成像(MRI)监测,从而改善TNBC的诊断和治疗效果。采用水热法制备了具有生物相容性和独特光学特性的CNSs,并在其上载荷DOX和Fe3O4,以获得Fe3O4 / DOX @ CNSs纳米系统。评估了Fe3O4 / DOX @ CNSs的形态学、水动力学大小、ζ电位和磁性等特征。通过不同pH / 近红外光能的释放来评估DOX的释放。在体内外检测了Fe3O4 @ CNSs,DOX和Fe3O4 / DOX @ CNSs的生物安全性、药代动力学、MRI和治疗。 Fe3O4 / DOX @ CNSs具有平均粒径160 nm和ζ电位27.5mV,表明Fe3O4 / DOX @ CNSs是一个稳定和均匀分散的系统。Fe3O4 / DOX @ CNSs的溶血实验证明了它可以在体内使用。Fe3O4 / DOX @ CNSs表现出高的光热转换效率和广泛的pH / 热诱导DOX释放。在pH = 5的PBS溶液中,808 nm激光下观察到70.3%的DOX释放,明显高于pH = 5(50.9%)和pH = 7.4(不到10%)。药代动力学实验表明,Fe3O4 / DOX @ CNSs的t1 / 2β和AUC0-t分别比DOX溶液高1.96和1.31倍。此外,具有NIR的Fe3O4 / DOX @ CNSs在体内外具有最大的肿瘤抑制率。此外,该纳米系统在T2 MRI上表现出明显的对比增强效果,以实现治疗期间的实时成像监测。Fe3O4 / DOX @ CNSs是一种高度生物相容性、双重触发和改善DOX生物利用度的纳米系统,结合化疗和光热治疗以及实时MRI监测,以实现TNBC的诊断和治疗的整合。 © 2023王等
Owing to lack of specific molecular targets, the current clinical therapeutic strategy for triple negative breast cancer (TNBC) is still limited. In recent years, some nanosystems for malignancy treatment have received considerable attention. In this study, we prepared caramelized nanospheres (CNSs) loaded with doxorubicin (DOX) and Fe3O4 to achieve the synergistic effect of combined therapy and real-time magnetic resonance imaging (MRI) monitoring, so as to improve the diagnosis and therapeutic effect of TNBC.CNSs with biocompatibility and unique optical properties were prepared by hydrothermal method, DOX and Fe3O4 were loaded on it to obtain Fe3O4/DOX@CNSs nanosystem. Characteristics including morphology, hydrodynamic size, zeta potentials and magnetic properties of Fe3O4/DOX@CNSs were evaluated. The DOX release was evaluated by different pH/near-infrared (NIR) light energy. Biosafety, pharmacokinetics, MRI and therapeutic treatment of Fe3O4@CNSs, DOX and Fe3O4/DOX@CNSs were examined in vitro or in vivo.Fe3O4/DOX@CNSs has an average particle size of 160 nm and a zeta potential of 27.5mV, it demonstrated that Fe3O4/DOX@CNSs is a stable and homogeneous dispersed system. The hemolysis experiment of Fe3O4/DOX@CNSs proved that it can be used in vivo. Fe3O4/DOX@CNSs displayed high photothermal conversion efficiency, extensive pH/heat-induced DOX release. 70.3% DOX release is observed under the 808 nm laser in the pH = 5 PBS solution, obviously higher than pH = 5 (50.9%) and pH = 7.4 (less than 10%). Pharmacokinetic experiments indicated the t1/2β, and AUC0-t of Fe3O4/DOX@CNSs were 1.96 and 1.31 -fold higher than those of DOX solution, respectively. Additionally, Fe3O4/DOX@CNSs with NIR had the greatest tumor suppression in vitro and in vivo. Moreover, this nanosystem demonstrated distinct contrast enhancement on T2 MRI to achieve real-time imaging monitoring during treatment.Fe3O4/DOX@CNSs is a highly biocompatible, double-triggering and improved DOX bioavailability nanosystem that combines chemo-PTT and real-time MRI monitoring to achieve integration of diagnosis and treatment of TNBC.© 2023 Wang et al.