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In Vivo Investigation of Hybrid Paclitaxel Nanocrystals with Dual Fluorescent Probes for Cancer Theranostics

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ABSTRACT

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

DLS:

Dynamic light scattering

MMP:

Matrix metalloproteinase

NIR:

Near infrared

PBS:

Phosphate buffered saline

PTX:

Paclitaxel

SEM:

Scanning electron microscope

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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.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, 40536, USA

    Christin P. Hollis

  2. Biostatistics, Division of Cancer Biostatistics, Markey Cancer Center, University of Kentucky, Lexington, Kentucky, 40506, USA

    Heidi L. Weiss

  3. Department of Surgery and Markey Cancer Center, University of Kentucky, Lexington, Kentucky, 40506, USA

    B. Mark Evers

  4. Departments of Biopharmaceutical Sciences, Bioengineering, and Ophthalmology and Visual Sciences, University of Illinois, Chicago, Illinois, 60612, USA

    Richard A. Gemeinhart

  5. Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, Heine Pharmacy Building, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907-2091, USA

    Tonglei Li

Authors
  1. Christin P. Hollis
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  2. Heidi L. Weiss
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  3. B. Mark Evers
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  4. Richard A. Gemeinhart
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  5. Tonglei Li
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Correspondence to Tonglei Li.

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Hollis, C.P., Weiss, H.L., Evers, B.M. et al. In Vivo Investigation of Hybrid Paclitaxel Nanocrystals with Dual Fluorescent Probes for Cancer Theranostics. Pharm Res 31, 1450–1459 (2014). https://doi.org/10.1007/s11095-013-1048-x

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  • DOI: https://doi.org/10.1007/s11095-013-1048-x

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