In Vivo Investigation of Hybrid Paclitaxel Nanocrystals with Dual Fluorescent Probes for Cancer Theranostics
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To develop novel hybrid paclitaxel (PTX) nanocrystals, in which bioactivatable (MMPSense® 750 FAST) and near infrared (Flamma Fluor® FPR-648) fluorophores are physically incorporated, and to evaluate their anticancer efficacy and diagnostic properties in breast cancer xenograft murine model.
The pure and hybrid paclitaxel nanocrystals were prepared by an anti-solvent method, and their physical properties were characterized. The tumor volume change and body weight change were evaluated to assess the treatment efficacy and toxicity. Bioimaging of treated mice was obtained non-invasively in vivo.
The released MMPSense molecules from the hybrid nanocrystals were activated by matrix metalloproteinases (MMPs) in vivo, similarly to the free MMPSense, demonstrating its ability to monitor cancer progression. Concurrently, the entrapped FPR-648 was imaged at a different wavelength. Furthermore, when administered at 20 mg/kg, the nanocrystal formulations exerted comparable efficacy as Taxol®, but with decreased toxicity.
Hybrid nanocrystals that physically integrated two fluorophores were successfully prepared from solution. Hybrid nanocrystals were shown not only exerting antitumor activity, but also demonstrating the potential of multi-modular bioimaging for diagnostics.
KEY WORDSbreast cancer MMPSense nanocrystals paclitaxel theranostics
Dynamic light scattering
Phosphate buffered saline
Scanning electron microscope
ACKNOWLEDGMENTS AND DISCLOSURES
The project described was supported by Grant Number R25CA153954 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.
- 23.Groves K, Kossodo S, Handy E, Jensen J, Blusztajn A, Cuneo G, et al. In vivo imaging of treatment effects using a novel near infrared labeled agent: MMPSense™ 750 FAST, AACR Annual Meeting, Denver, 2009.Google Scholar