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

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

Lu Y1,2, Li L2,3, Lin Z2, Li M2, Hu X2, Zhang Y2, Peng M3, Xia H2, Han G4.

Author information

1
Department of Orthopedics, Zhujiang Hospital, Southern Medical University, 253 Gongye Road, Guangzhou, 510282, China.
2
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.
3
China-Germany Research Center for Photonic Materials and Device, the State Key Laboratory of Luminescent Materials and Devices, School of Materials Science and Engineering, South China University of Technology, 381 Wushan Road, Guangzhou, 510641, China.
4
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, 01605, USA.

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 (Bi2 S3 @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 Bi2 S3 @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-2 ). 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-Bi2 S3 @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-Bi2 S3 @MSN/DOX theranostic platform is a promising candidate for future applications in CT monitoring and synergistic treatment of malignant tumors.

KEYWORDS:

Bi2S3@MSN; X-ray computed tomography; mitochondrial apoptosis pathway; osteosarcoma; photothermal therapy-chemotherapy

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