Intravenously-injected gold nanoparticles (AuNPs) access intracerebral F98 rat gliomas better than AuNPs infused directly into the tumor site by convection enhanced delivery

静脉注射的金纳米粒子 (AuNP) 比通过对流增强输送直接注入肿瘤部位的 AuNP 更能进入 F98 大鼠脑内神经胶质瘤

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作者:Henry M Smilowitz, Alexandria Meyers, Khalil Rahman, Nathaniel A Dyment, Dan Sasso, Crystal Xue, Douglas L Oliver, Alexander Lichtler, Xiaomeng Deng, Sharif M Ridwan, Lauren J Tarmu, Qian Wu, Andrew L Salner, Ketan R Bulsara, Daniel N Slatkin, James F Hainfeld

Background

Intravenously (IV)-injected gold nanoparticles (AuNPs) powerfully enhance the efficacy of X-ray therapy of tumors including advanced gliomas. However, pharmacokinetic issues, such as slow tissue clearance and skin discoloration, may impede clinical translation. The direct infusion of AuNPs into the tumor might be an alternative mode of delivery. Materials and

Conclusion

These data suggest that IV-injected AuNPs are likely to have a greater therapeutic benefit when combined with radiation therapy than after the direct infusion of AuNPs.

Methods

Using the advanced, invasive, and difficult-to-treat F98 rat glioma model, we have studied the biodistribution of the AuNPs in the tumor and surrounding brain after either IV injection or direct intratumoral infusion by convection-enhanced delivery using light microscopy immunofluorescence and direct gold visualization.

Results

IV-injected AuNPs localize more specifically to intracerebral tumor cells, both in the main tumor mass and in the migrated tumor cells as well as the tumor edema, than do the directly infused AuNPs. Although some of the directly infused AuNPs do access the main tumor region, such access is largely restricted.

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