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仿生策略构建高效入胞脂质体纳米递药系统增强癌症化疗

Highly penetrative liposome nanomedicine generated by a biomimetic strategy for enhanced cancer chemotherapy.

机构信息

Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China.

出版信息

Biomater Sci. 2018 May 29;6(6):1546-1555. doi: 10.1039/c8bm00256h.

Abstract

Liposome nanomedicine has been successfully applied for cancer chemotherapy in patients. However, in general, the therapeutic efficacy is confined by its limited accumulation and penetration in solid tumors. Here, we established a biomimetic strategy for the preparation of highly penetrative liposome nanomedicine for enhanced chemotherapeutic efficacy. By applying this unique type of nanomedicine, membrane proteins on the cancer cells are used as highly penetrative targeting ligands. Biomimetic liposomes are highly stable, exhibiting a superior in vitro homologous targeting ability, and a 2.25-fold deeper penetration in 3D tumor spheroids when compared to conventional liposome nanomedicine. The fluorescence/photoacoustic dual-modal imaging approach demonstrated enhanced tumor accumulation and improved tumor penetration of the biomimetic liposome in C6 glioma tumor-bearing nude mice. Following the intravenous administration of biomimetic liposome nanomedicine, the tumor inhibition rate reached up to 93.3%, which was significantly higher when compared to that of conventional liposome nanomedicine (69.3%). Moreover, histopathological analyses demonstrated that biomimetic liposome nanomedicine has limited side effects. Therefore, these results suggested that a cancer cell membrane-based biomimetic strategy may provide a breakthrough approach for enhancing drug penetration and improving treatment efficacy, holding a great promise for further clinical studies.

摘要

脂质体纳米医学已成功应用于癌症患者的化疗。然而,总的来说,其在实体瘤中的积累和渗透有限,限制了其治疗效果。在这里,我们建立了一种仿生策略,用于制备高渗透性脂质体纳米医学,以增强化疗效果。通过应用这种独特类型的纳米医学,癌细胞上的膜蛋白被用作高渗透性靶向配体。仿生脂质体非常稳定,表现出优越的体外同源靶向能力,并且在 3D 肿瘤球体中的渗透深度增加了 2.25 倍,与传统脂质体纳米医学相比。荧光/光声双模成像方法表明,仿生脂质体在 C6 神经胶质瘤荷瘤裸鼠中具有增强的肿瘤积累和改善的肿瘤渗透。静脉注射仿生脂质体纳米医学后,肿瘤抑制率高达 93.3%,明显高于传统脂质体纳米医学(69.3%)。此外,组织病理学分析表明,仿生脂质体纳米医学的副作用有限。因此,这些结果表明,基于癌细胞膜的仿生策略可能为增强药物渗透和提高治疗效果提供突破途径,具有很大的临床研究前景。

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