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Nano Research

, Volume 10, Issue 4, pp 1366–1376 | Cite as

Targeting orthotopic gliomas with renal-clearable luminescent gold nanoparticles

  • Chuanqi Peng
  • Xiaofei Gao
  • Jing Xu
  • Bujie Du
  • Xuhui Ning
  • Shaoheng Tang
  • Robert M. Bachoo
  • Mengxiao Yu
  • Woo-Ping Ge
  • Jie Zheng
Research Article

Abstract

A major clinical translational challenge in nanomedicine is the potential of toxicity associated with the uptake and long-term retention of non-degradable nanoparticles (NPs) in major organs. The development of inorganic NPs that undergo renal clearance could potentially resolve this significant biosafety concern. However, it remains unclear whether inorganic NPs that can be excreted by the kidneys remain capable of targeting tumors with poor permeability. Glioblastoma multiforme, the most malignant orthotopic brain tumor, presents a unique challenge for NP delivery because of the blood-brain barrier and robust blood-tumor barrier of reactive microglia and macroglia in the tumor microenvironment. Herein, we used an orthotopic murine glioma model to investigate the passive targeting of glutathione-coated gold nanoparticles (AuNPs) of 3 nm in diameter that undergo renal clearance and 18-nm AuNPs that fail to undergo renal clearance. Remarkably, we report that 3-nm AuNPs were able to target intracranial tumor tissues with higher efficiency (2.3× relative to surrounding non-tumor normal brain tissues) and greater specificity (3.0×) than did the larger AuNPs. Pharmacokinetics studies suggested that the higher glioma targeting ability of the 3-nm AuNPs may be attributed to the longer retention time in circulation. The total accumulation of the 3-nm AuNPs in major organs was significantly less (8.4×) than that of the 18-nm AuNPs. Microscopic imaging of blood vessels and renal-clearable AuNPs showed extravasation of NPs from the leaky blood-tumor barrier into the tumor interstitium. Taken together, our results suggest that the 3-nm AuNPs, characterized by enhanced permeability and retention, are able to target brain tumors and undergo renal clearance.

Keywords

enhanced permeability and retention brain tumor passive targeting gold nanoparticles renal clearance 

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Notes

Acknowledgements

This study was partially supported by CPRIT (Nos. RP140544 and RP160866), NIH (No. 1R01DK103363) and a start-up fund from the University of Texas at Dallas to J. Z., UTSW CRI start-up funds, UTSW High Impact/High Risk Grant and NINDS K99/R00 (No. R00NS073735) to W. P. G.

Supplementary material

12274_2017_1472_MOESM1_ESM.pdf (731 kb)
Targeting orthotopic gliomas with renal-clearable luminescent gold nanoparticles

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Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Chuanqi Peng
    • 1
  • Xiaofei Gao
    • 2
  • Jing Xu
    • 1
  • Bujie Du
    • 1
  • Xuhui Ning
    • 1
  • Shaoheng Tang
    • 1
  • Robert M. Bachoo
    • 3
  • Mengxiao Yu
    • 1
  • Woo-Ping Ge
    • 2
  • Jie Zheng
    • 1
  1. 1.Department of Chemistry and BiochemistryThe University of Texas at DallasRichardsonUSA
  2. 2.Children’s Research Institute, Department of Pediatrics, Department of Neuroscience, Harold C. Simmons Comprehensive Cancer CenterUT Southwestern Medical CenterDallasUSA
  3. 3.Simmons Cancer Center, Annette G. Strauss Center for Neuro-Oncology, Department of Internal Medicine, Department of Neurology and NeurotherapeuticsUT Southwestern Medical CenterDallasUSA

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