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

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 (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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bismuth / chemistry*
  • Cell Line, Tumor
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Mice
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Oligopeptides / chemistry
  • Osteosarcoma / diagnostic imaging*
  • Osteosarcoma / drug therapy*
  • Porosity
  • Rats
  • Silicon Dioxide / chemistry*
  • Sulfides / chemistry*
  • Tomography, X-Ray Computed / methods*

Substances

  • Oligopeptides
  • Sulfides
  • Silicon Dioxide
  • arginyl-glycyl-aspartic acid
  • Doxorubicin
  • Bismuth
  • bismuth sulfide