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Real-time monitoring of in vivo site-specific exposure of Doxorubicin using NIR-II emission of SWCNTs

The majority of chemotherapy drugs, despite their efficacy in annihilating cancer cells, are known to have unmanageable and irreversible side effects that preclude their use in higher doses. Understanding fluctuations in drug distribution and monitoring cumulative toxicity in different locations is essential for the assessment of patient-specific dose limits.

In a recent study[1] performed by the Heller group at Memorial Sloan Kettering Cancer Center, real-time monitoring and quantification of doxorubicin, a chemotherapy drug effective against rapid cell division, was performed both in vitro and in vivo using IMA™ hyperspectral microscope and IR VIVO™ preclinical imager.

Detection of doxorubicin was achieved using an implantable sensor based on DNA-suspended carbon nanotubes developed by the Heller group. Fluorescence measurements were acquired through the skin using Photon etc.’s near-infrared preclinical hyperspectral imager, IR VIVO™. Results presented in Figure 1. show that wavelength shifts in sensor emission allow quantitative detection of doxorubicin and its cumulative toxicity within the peritoneal area.

Fig. 1 | The binding of doxorubicin to single-walled carbon nanotubes (SWCNTs) results in a red-shifted and quenched emission of nanotube photoluminescence. a) Schematic overview of SWCNT sensor implanted inside and outside the peritoneal cavity. b) Spectral emission of implanted sensors before (dark blue curve) and after (light blue curve) injection of doxorubicin. c) Periodic monitoring of center wavelength emission of the sensor inside the peritoneal cavity after injection.

The ability to perform rapid pharmacokinetic analysis in vivo has the potential to significantly facilitate preclinical studies, by monitoring drug biodistribution over time in a single animal instead of dissecting a different animal at each time frame. Clinically, a cumulative sensor could help to predict patient-specific lifetime dose limits by monitoring drug biodistribution. This could reduce the incidence of adverse effects such as cardiotoxicity.

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[1] Harvey, J. D., Williams, R. M., Tully, K. M., Baker, H. A., Shamay, Y., & Heller, D. A. (2019). An in Vivo Nanosensor Measures Compartmental Doxorubicin Exposure. Nano Letters, 19(7), 4343–4354.


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