4.7 Article

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

Journal

ADVANCED HEALTHCARE MATERIALS
Volume 7, Issue 19, Pages -

Publisher

WILEY
DOI: 10.1002/adhm.201800602

Keywords

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

Funding

  1. National Key Research Program of China [2017YFB0702604]
  2. National Natural Science Foundation of China [31771038, 81402409]
  3. Fundamental Research Funds for the Central Universities
  4. Hundred, Thousand and Ten Thousand Leading Talent Project in Guangdong Program for Special Support of Eminent Professionals
  5. Natural Science Foundation of Guangdong Province, China [2015A030312004]
  6. Scientific and Technological Projects of Guangzhou, China [201604020110]
  7. National Institutes of Health [R01MH103133, R21GM126532]

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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 (Bi2S3 @ 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 Bi2S3 @ 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-Bi2S3 @ 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-Bi2S3 @ MSN/DOX theranostic platform is a promising candidate for future applications in CT monitoring and synergistic treatment of malignant tumors.

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