Tumor Angiogenesis Targeted Radiosensitization Therapy Using Gold Nanoprobes Guided by MRI/SPECT Imaging.

Abstract

Gold nanoparticles (AuNPs) have recently garnered great interest as potential radiosensitizers in tumor therapy. However, major challenges facing their application in this regard are further enhancement of tumor accumulation of the particles in addition to enhanced permeability retention (EPR) effect and an understanding of the optimal particle size and time for applying radiotherapy after the particle administration. In this study, we fabricated novel cyclic c(RGDyC)-peptide-conjugated, Gd- and 99 mTc-labeled AuNPs (RGD@AuNPs-Gd99 mTc) probes with different sizes (29, 51, and 80 nm) and evaluated their potential as radiosensitization therapy both in vitro and in vivo. We found that these probes have a high specificity for αvβ3 integrin positive cells, which resulted in their high cellular uptake and thereby enhanced radiosensitization. Imaging in vivo with MRI and SPECT/CT directly showed that the RGD@AuNPs-Gd99 mTc probes specifically target tumors and exhibit greater accumulation within tumors than the RAD@AuNPs-Gd99 mTc probes. Interestingly, we found that the 80 nm RGD@AuNPs-Gd99 mTc probes exhibit the greatest effects in vitro; however, the 29 nm RGD@AuNPs-Gd99 mTc probes were clearly most efficient in vivo. As a result, radiotherapy of tumors with the 29 nm probe was the most potent. Our study demonstrates that RGD@AuNPs-Gd99 mTc probes are highly useful radiosensitizers capable of guiding and enhancing radiation therapy of tumors.

• Authors: Yi Yang, Lu Zhang, Jiali Cai, Xiao Li, Dengfeng Cheng, Huilan Su, Jianping Zhang, Shiyuan Liu, Hongcheng Shi, Yingjian Zhang, Chunfu Zhang
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 8 Issue 3 Pg. 1718-32 (Jan 27 2016) ISSN: 1944-8252 [Electronic] United States
• PMID: 26731347 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Integrin alphaVbeta3
• Oligopeptides
• Technetium
• Gold
• arginyl-glycyl-aspartic acid
• Gadolinium

Topics

• Animals
• Cell Death (drug effects)
• Cell Line, Tumor
• Gadolinium (chemistry)
• Gold (chemistry, toxicity)
• Humans
• Immunohistochemistry
• Integrin alphaVbeta3
• Magnetic Resonance Imaging
• Metal Nanoparticles (chemistry, toxicity)
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasms (blood supply, pathology, radiotherapy)
• Neovascularization, Pathologic (therapy)
• Oligopeptides (chemistry)
• Radiation Tolerance
• Subcellular Fractions (metabolism)
• Technetium (chemistry)
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon