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首页> 外文期刊>Advanced Functional Materials >Triphenylphosphonium-Conjugated Poly(epsilon-caprolactone)-Based Self-Assembled Nanostructures as Nanosized Drugs and Drug Delivery Carriers for Mitochondria-Targeting Synergistic Anticancer Drug Delivery
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Triphenylphosphonium-Conjugated Poly(epsilon-caprolactone)-Based Self-Assembled Nanostructures as Nanosized Drugs and Drug Delivery Carriers for Mitochondria-Targeting Synergistic Anticancer Drug Delivery

机译：三苯基phosph缀合的聚（ε-己内酯）的自组装纳米结构作为纳米药物和线粒体靶向协同抗癌药物传递的药物传递载体。

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摘要

For mitochondria-targeting delivery, a coupling reaction between poly(epsilon-caprolactone) diol (PCL diol) and 4-carboxybutyltriphenylphosphonium (4-carboxybutyl TPP) results in the synthesis of amphiphilic TPP-PCL-TPP (TPCL) polymers with a bola-like structure. In aqueous environments, the TPCL polymer self-assembled via cosolvent dispersion and film hydration, resulting in the formation of cationic nanoparticles (NPs) less than 50 nm in size with zeta-potentials of approximately 40 mV. Interestingly, different preparation methods for TPCL NPs result in various morphologies such as nanovesicles, nanofibers, and nanosheets. In vitro cytotoxicity results with TPCL NPs indicate IC50 values of approximately 10-60 g mL(-1), suggesting their potential as anticancer nanodrugs. TPCL NPs can be loaded both with hydrophobic doxorubicin (Dox) and its hydrophilic salt form (DoxHCl), and their drug loading contents are approximately 2-10 wt% depending on the loading method and the hydrophilicity/hydrophobicity of the drugs. Although DoxHCl exhibits more cellular and nuclear uptake, resulting in greater antitumor effects than Dox, most drug-loaded TPCL NPs exhibit higher mitochondrial uptake and approximately 2-7-fold higher mitochondria-to-nucleus preference than free drugs, resulting in superior (approximately 7.5-18-fold) tumor-killing activity for most drug-loaded TPCL NPs compared with free drugs. In conclusion, TPCL-based nanoparticles have potential both as antitumor nanodrugs themselves and as nanocarriers for chemical therapeutics.
机译：对于线粒体靶向递送，聚（ε-己内酯）二醇（PCL二醇）与4-羧基丁基三苯基phosph（4-羧基丁基TPP）之间的偶联反应导致两亲TPP-PCL-TPP（TPCL）聚合物与像结构。在水性环境中，TPCL聚合物通过助溶剂分散和膜水合作用而自组装，导致形成尺寸小于50 nm，ζ电势约为40 mV的阳离子纳米粒子（NP）。有趣的是，TPCL NP的不同制备方法会导致各种形态，例如纳米囊泡，纳米纤维和纳米片。 TPCL NPs的体外细胞毒性结果表明IC50值约为10-60 g mL（-1），表明它们作为抗癌纳米药物的潜力。 TPCL NP既可以负载疏水性阿霉素（Dox），也可以负载其亲水性盐形式（DoxHCl），其负载量取决于负载方法和药物的亲水性/疏水性，约为2-10 wt％。尽管DoxHCl与Dox相比具有更多的细胞和核吸收特性，因此具有更大的抗肿瘤作用，但大多数载药的TPCL NPs的线粒体吸收性更高，线粒体至细胞核的自由度约为游离药物的2-7倍，从而产生了更好的（大约）与游离药物相比，大多数载有TPCL NP的肿瘤杀伤活性为7.5-18倍。总之，基于TPCL的纳米颗粒既有作为抗肿瘤纳米药物本身的潜力，也有作为化学治疗方法的纳米载体的潜力。

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  • 来源
    《Advanced Functional Materials》 |2015年第34期|5479-5491|共13页
  • 作者

    Cho Dong Youl; Cho Hana; Kwon Kiyoon; Yu Minjong; Lee Eunji; Huh Kang Moo; Lee Don Haeng; Kang Han Chang;

  • 作者单位

    Catholic Univ Korea, Coll Pharm, Dept Pharm & Integrated Res, Inst Pharmaceut Sci, Bucheon Si 420743, Gyeonggi Do, South Korea;

    Catholic Univ Korea, Coll Pharm, Dept Pharm & Integrated Res, Inst Pharmaceut Sci, Bucheon Si 420743, Gyeonggi Do, South Korea;

    Catholic Univ Korea, Coll Pharm, Dept Pharm & Integrated Res, Inst Pharmaceut Sci, Bucheon Si 420743, Gyeonggi Do, South Korea;

    Chungnam Natl Univ, Grad Sch Analyt Sci & Technol, Taejon 305764, South Korea;

    Chungnam Natl Univ, Grad Sch Analyt Sci & Technol, Taejon 305764, South Korea;

    Chungnam Natl Univ, Dept Polymer Sci & Engn, Taejon 305764, South Korea;

    Inha Univ Hosp, Dept Internal Med, Div Gastroenterol & Hepatol, Inchon 400712, South Korea|Utah Inha Drug Delivery Syst & Adv Therapeut Res, Inchon 406840, South Korea;

    Catholic Univ Korea, Coll Pharm, Dept Pharm & Integrated Res, Inst Pharmaceut Sci, Bucheon Si 420743, Gyeonggi Do, South Korea;

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  • 关键词

    mitochondria-targeting drug delivery; poly(epsilon-caprolactone); self-assembled nanomedicine; subcellular targeting; triphenylphosphonium;

    机译：线粒体靶向药物递送;聚己内酯;自组装纳米药物;亚细胞靶向;三苯基phosph;

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