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利用超高载药量和近红外响应的硫化铋@介孔硅纳米粒子增强骨肉瘤杀伤和 CT 成像。

Enhancing Osteosarcoma Killing and CT Imaging Using Ultrahigh Drug Loading and NIR-Responsive Bismuth Sulfide@Mesoporous Silica Nanoparticles.

机构信息

Department of Orthopedics, Zhujiang Hospital, Southern Medical University, 253 Gongye Road, Guangzhou, 510282, China.

Department of Orthopedics, Guangdong Key Lab of Orthopedic Technology and Implant, Key Laboratory of Trauma & Tissue Repair of Tropical Area of PLA, Guangzhou General Hospital of Guangzhou Military Command of PLA, 111 Liuhua Road, Guangzhou, Guangdong, 510010, China.

出版信息

Adv Healthc Mater. 2018 Oct;7(19):e1800602. doi: 10.1002/adhm.201800602. Epub 2018 Aug 13.

Abstract

Despite its 5-year event-free survival rate increasing to 60-65% due to surgery and chemotherapy, osteosarcoma (OS) remains one of the most threatening malignant human tumors, especially in young patients. Therefore, a new approach that combines early diagnosis with efficient tumor eradication and bioimaging is urgently needed. Here, a new type of mesoporous silica-coated bismuth sulfide nanoparticles (Bi S @MSN NPs) is developed. The well distributed mesoporous pores and large surface areas hold great promise for drug protection and encapsulation (doxorubicin (DOX), 99.85%). Moreover, the high photothermal efficiency of Bi S @MSNs (36.62%) offers great possibility for cancer synergistic treatment and highly near-infrared-triggered drug release (even at an ultralow power density of 0.3 W cm ). After covalently conjugated to arginine-glycine-aspartic acid (RGD) peptide [c(RGDyC)], the NPs exhibit a high specificity for osteosarcoma and finally accumulate in the tumor cells (tenfold more than peritumoral tissues) for computed tomography (CT) imaging and tumor ablation. Importantly, the synergistic photothermal therapy-chemotherapy of the RGD-Bi S @MSN/DOX significantly ablates the highly malignant OS. It is further proved that the superior combined killing effect is achieved by activating the mitochondrial apoptosis pathway. Hence, the smart RGD-Bi S @MSN/DOX theranostic platform is a promising candidate for future applications in CT monitoring and synergistic treatment of malignant tumors.

摘要

尽管手术和化疗使骨肉瘤(OS)的 5 年无事件生存率提高到 60-65%,但它仍然是威胁人类健康的最具侵袭性的恶性肿瘤之一,尤其是在年轻患者中。因此,迫切需要一种新的方法,将早期诊断与高效的肿瘤消除和生物成像相结合。在这里,开发了一种新型的介孔硅包覆的硫化铋纳米粒子(Bi S@MSN NPs)。均匀分布的介孔孔和大的表面积为药物保护和封装(阿霉素(DOX),99.85%)提供了巨大的可能性。此外,Bi S@MSNs 的高光热效率(36.62%)为癌症协同治疗和高近红外触发药物释放提供了巨大的可能性(即使在超低功率密度为 0.3 W cm-2 时)。与精氨酸-甘氨酸-天冬氨酸(RGD)肽[c(RGDyC)]共价连接后,纳米粒子对骨肉瘤表现出很高的特异性,最终在肿瘤细胞中积累(比肿瘤周围组织多十倍),用于计算机断层扫描(CT)成像和肿瘤消融。重要的是,RGD-Bi S@MSN/DOX 的协同光热化疗显著消融了高度恶性的 OS。进一步证明,通过激活线粒体凋亡途径实现了优越的联合杀伤效果。因此,智能 RGD-Bi S@MSN/DOX 治疗平台是未来用于 CT 监测和协同治疗恶性肿瘤的有前途的候选者。

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