Editors' ChoiceNANOSCIENCE

Theranostic nanoparticles give the best of both worlds

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Science Translational Medicine  20 Jul 2016:
Vol. 8, Issue 348, pp. 348ec114
DOI: 10.1126/scitranslmed.aah3547

The delivery of therapeutics into tumors poses a number of challenges, including leaky neovascular networks that feed cancer cells, dense stroma associated with many tumors, and acidic interstitial spaces that act to reduce drug delivery. Theranostics—agents that have both therapeutic and diagnostic capabilities—can significantly aid in the optimization of drug delivery and provide a means for creating more effective treatments.

In a recent study, Liu et al. successfully treated mouse models of anaplastic thyroid cancer (ATC) using a new theranostic nanoparticle platform. ATC is a devastating disease with no effective therapy and an approximate 100% mortality rate, where metastasis is typically driven by mutations in key oncogenes such as BRAF and TP53. Given the dependence of the cancer on these activating mutations, there is opportunity for gene silencing therapies such as small interfering RNA (siRNA) to provide a cure. To treat these tumors, the authors created theranostic nanoparticles built from conjugated near-infrared fluorescent polymers to selectively deliver siRNAs and simultaneously enable tracking of the agent's uptake and distribution on the cellular, tumor, and whole-body scales.

Starting in vitro, the authors demonstrated that their nanoparticle system could be loaded with siRNA to specifically and effectively silence genes of interest. Importantly, when delivered in vivo, the bright fluorescence afforded by the polymeric nanoparticle enabled whole body mapping of the theranostic agent's biodistribution, in particular into both implanted tumors and their metastases within the lungs and lymph nodes. Three treatments of the theranostic nanoparticles targeting BRAF expression were effective in reducing the growth rate of implanted ATC xenografts, demonstrating the promise of this new nanoparticle platform. Although tumors are likely to overcome the specific inhibition of activating mutations, the theranostic approach does offer the ability to track and therefore create individual and personalized treatments, especially for lethal diseases such as ATC.

Y. Liu et al., Theranostic near-infrared fluorescent nanoplatform for imaging and systemic siRNA delivery to metastatic anaplastic thyroid cancer. Proc. Natl. Acad. Sci. U.S.A. 113, 7750–7755 (2016). [Abstract]

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