Journal
THERANOSTICS
Volume 10, Issue 3, Pages 1319-1331Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.37543
Keywords
theranostic; ultrasmall nanoparticle; EPR effect; clinical translation; AGuIX
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Interest of tumor targeting through EPR effect is still controversial due to intrinsic low targeting efficacy and rare translation to human cancers. Moreover, due to different reasons, it has generally been described for relatively large nanoparticles (NPs) (hydrodynamic diameter > 10 nm). In this review EPR effect will be discussed for ultrasmall NPs using the example of the AGuIX (R) NP (Activation and Guiding of Irradiation by X-ray) recently translated in clinic. AGuIX (R) NP is a 4 +/- 2 nm hydrodynamic diameter polysiloxane based NP. Since AGuIX (R) NP biodistribution is monitored by magnetic resonance imaging (MRI) and its activation is triggered by irradiation upon X-rays, this NP is well adapted for a theranostic approach of radiotherapy cancer treatment. Here we show that AGuIX (R) NP is particularly well suited to benefit from EPR-mediated tumor targeting thanks to an ultrasmall size and efficacy under irradiation at small dose. Indeed, intravenously-injected AGuIX (R) NP into rodent cancer models passively reached the tumor and revealed no toxicity, favoured by renal clearance. Moreover, translation of AGuIX (R) NP accumulation and retention into humans carrying brain metastases was validated during a first-in-man phase lb trial taking advantage of easy biodistribution monitoring by MRI.
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