Research Paper

Pharmaceutical Research

, Volume 31, Issue 6, pp 1450-1459

First online:

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

  • Christin P. HollisAffiliated withDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky
  • , Heidi L. WeissAffiliated withBiostatistics, Division of Cancer Biostatistics, Markey Cancer Center, University of Kentucky
  • , B. Mark EversAffiliated withDepartment of Surgery and Markey Cancer Center, University of Kentucky
  • , Richard A. GemeinhartAffiliated withDepartments of Biopharmaceutical Sciences, Bioengineering, and Ophthalmology and Visual Sciences, University of Illinois
  • , Tonglei LiAffiliated withDepartment of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University Email author 

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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.

KEY WORDS

breast cancer MMPSense nanocrystals paclitaxel theranostics