Photophysical characterization of anticancer drug valrubicin in rHDL nanoparticles and its use as an imaging agent.
Photophysical characterization of anticancer drug valrubicin in rHDL nanoparticles and its use as an imaging agent.
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DOI：
10.1016/j.jphotobiol.2015.12.007
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Gryczynski I
中科院分区：
文献类型：
--
作者：
Shah S;Chib R;Raut S;Bermudez J;Sabnis N;Duggal D;Kimball JD;Lacko AG;Gryczynski Z;Gryczynski I
纳米颗粒是靶向特异性药物递送剂，越来越多地用于癌症治疗，以提高抗癌药物的生物利用度并减少脱靶毒性。 Valrubicin 是一种抗癌药物，由于其水溶性差，目前仅被批准用于水泡性膀胱癌的治疗。另一方面，携带重组高密度脂蛋白（rHDL）纳米颗粒的戊柔比星似乎非常适合扩展应用，包括全身癌症化疗。我们确定了游离（未封装的）药物与掺入 rHDL 纳米颗粒中的戊柔比星的选定荧光特性。我们发现，封装到 rHDL 纳米颗粒中后，戊柔比星荧光的量子产率增加了六倍，而其荧光寿命增加了约 2 倍。因此，这些和碘化钾 (KI) 猝灭数据表明，掺入后，戊柔比星位于纳米颗粒内部深处，即脂质基质内。随着旋转相关时间的延长，rHDL 戊柔比星纳米颗粒的荧光各向异性也很高。戊柔比星的荧光也可用于评估其在递送至前列腺癌 (PC3) 细胞后的分布。总体而言，rHDL：戊柔比星复合物的荧光特性揭示了这种药物递送载体的有价值的新特征，这些特征在用于全身（静脉）治疗时可能特别适用。
Nanoparticles are target-specific drug delivery agents that are increasingly used in cancer therapy to enhance bioavailability and to reduce off target toxicity of anti-cancer agents. Valrubicin is an anti-cancer drug, currently approved only for vesicular bladder cancer treatment because of its poor water solubility. On the other hand, valrubicin carrying reconstituted high density lipoprotein (rHDL) nanoparticles appear ideally suited for extended applications, including systemic cancer chemotherapy. We determined selected fluorescence properties of the free (unencapsulated) drug vs. valrubicin incorporated into rHDL nanoparticles. We have found that upon encapsulation into rHDL nanoparticles the quantum yield of valrubicin fluorescence increased six fold while its fluorescence lifetime increased about 2 fold. Accordingly, these and potassium iodide (KI) quenching data suggest that upon incorporation, valrubicin is localized deep in the interior of the nanoparticle, inside the lipid matrix. Fluorescence anisotropy of the rHDL valrubicin nanoparticles was also found to be high along with extended rotational correlation time. The fluorescence of valrubicin could also be utilized to assess its distribution upon delivery to prostate cancer (PC3) cells. Overall the fluorescence properties of the rHDL: valrubicin complex reveal valuable novel characteristics of this drug delivery vehicle that may be particularly applicable when used in systemic (intravenous) therapy.
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