title: In vivo investigation of hybrid Paclitaxel nanocrystals with dual fluorescent probes for cancer theranostics.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, 40536, USA.
authors.forename: Christin P
authors.initials: CP
authors.lastname: Hollis
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Weiss
authors.forename: B Mark
authors.initials: BM
authors.lastname: Evers
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gemeinhart
authors.forename: Tonglei
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005456:Fluorescent Dyes; D020782:Matrix Metalloproteinases; D017239:Paclitaxel