Hollis Christin P, Weiss Heidi L, Evers B Mark, Gemeinhart Richard A, Li Tonglei
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, 40536, USA.
Pharm Res. 2014 Jun;31(6):1450-9. doi: 10.1007/s11095-013-1048-x. Epub 2013 Apr 26.
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.
开发新型混合紫杉醇（PTX）纳米晶体，其中生物可激活（MMPSense® 750 FAST）和近红外（Flamma Fluor® FPR - 648）荧光团被物理包埋，并在乳腺癌异种移植小鼠模型中评估其抗癌疗效和诊断特性。
通过反溶剂法制备纯紫杉醇纳米晶体和混合紫杉醇纳米晶体，并对其物理性质进行表征。评估肿瘤体积变化和体重变化以评估治疗效果和毒性。在体内对治疗后的小鼠进行无创生物成像。
混合纳米晶体释放的MMPSense分子在体内被基质金属蛋白酶（MMPs）激活，与游离的MMPSense类似，证明其监测癌症进展的能力。同时，包埋的FPR - 648在不同波长下成像。此外，当以20 mg/kg给药时，纳米晶体制剂发挥了与紫杉醇相当的疗效，但毒性降低。
成功从溶液中制备了物理整合两种荧光团的混合纳米晶体。混合纳米晶体不仅显示出抗肿瘤活性，还展示了用于诊断的多模块生物成像潜力。
