Pharmaceutical Research

, Volume 31, Issue 6, pp 1450–1459 | Cite as

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

  • Christin P. Hollis
  • Heidi L. Weiss
  • B. Mark Evers
  • Richard A. Gemeinhart
  • Tonglei Li
Research Paper

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.

KEY WORDS

breast cancer MMPSense nanocrystals paclitaxel theranostics 

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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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Christin P. Hollis
    • 1
  • Heidi L. Weiss
    • 2
  • B. Mark Evers
    • 3
  • Richard A. Gemeinhart
    • 4
  • Tonglei Li
    • 5
  1. 1.Department of Pharmaceutical Sciences, College of PharmacyUniversity of KentuckyLexingtonUSA
  2. 2.Biostatistics, Division of Cancer Biostatistics, Markey Cancer CenterUniversity of KentuckyLexingtonUSA
  3. 3.Department of Surgery and Markey Cancer CenterUniversity of KentuckyLexingtonUSA
  4. 4.Departments of Biopharmaceutical Sciences, Bioengineering, and Ophthalmology and Visual SciencesUniversity of IllinoisChicagoUSA
  5. 5.Department of Industrial and Physical Pharmacy, College of PharmacyPurdue UniversityWest LafayetteUSA

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