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

Abstract

BackgroundIntravenously (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 methodsUsing 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.ResultsIV-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.ConclusionThese 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.

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A gain of function paradox: Targeted therapy for glioblastoma associated with abnormal NHE9 expression

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“…31 intravenous injection of GNPs has better therapeutic benefit than direct infusion of GNPs into the tumour. 33 GNPs accumulate in tumours via enhanced permeability and retention effect by passing through compromised endothelial tumour vasculature, especially during the later stages of the cancer. 34 GNPs directly infused into the tumour diffuse in the interstitial space around the tumour cells without any tumour cell-specific localization.…”

Novel Iodine nanoparticles target vascular mimicry in intracerebral triple negative human MDA-MB-231 breast tumors

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