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Synthesis of a drug delivery vehicle for cancer treatment utilizing DNA-functionalized gold nanoparticles.

机译：利用DNA功能化的金纳米粒子合成用于癌症治疗的药物递送载体。

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摘要

The treatment of cancer with chemotherapeutic agents has made great strides in the last few decades but still introduces major systemic side effects. The potent drugs needed to kill cancer cells often cause irreparable damage to otherwise healthy organs leading to further morbidity and mortality. A therapy with intrinsic selective properties and/or an inducible activation has the potential to change the way cancer can be treated. Gold nanoparticles (GNPs) are biocompatible and chemically versatile tools that can be readily functionalized to serve as molecular vehicles. The ability of these particles to strongly absorb light with wavelengths in the therapeutic window combined with the heating effect of surface plasmon resonance makes them uniquely suited for noninvasive heating in biologic applications. Specially designed DNA aptamers have shown their ability to serve as drug carriers through intercalation as well as directly acting as therapeutic agents. By combining these separate molecules a multifaceted drug delivery vehicle can be created with great potential as a selective and controllable treatment for cancer.;Oligonucleotide-coated GNPs have been created using spherical GNPs but little work has been reported using gold nanoplates in this way. Using the Diasynth method gold nanoplates were produced to absorb strongly in the therapeutic near infrared (nIR) window. These particles were functionalized with two DNA oligonucleotides: one serving as an intercalation site for doxorubicin, and another, AS1411, serving directly as an anticancer targeting/therapeutic agent. These functional particles were fully synthesized and processed along with confirmation of DNA functionalization and doxorubicin intercalation. Doxorubicin is released via denaturation of the DNA structure into which doxorubicin is intercalated upon the heating of the gold nanoplate well above the DNA melting temperature. This temperature increase, due to light stimulation of surface plasmon resonance, was measured during laser application. Successful release of doxorubicin via laser application was measured with fluorescence measurements providing proof that the doxorubicin was successfully intercalated and released.
机译：在过去的几十年中，使用化学治疗剂治疗癌症取得了长足的进步，但仍带来了主要的全身性副作用。杀死癌细胞所需的有效药物通常会对原本健康的器官造成无法弥补的损害，从而导致进一步的发病率和死亡率。具有内在选择性和/或可诱导激活的疗法有可能改变癌症的治疗方式。金纳米颗粒（GNP）是生物相容性和化学用途广泛的工具，可以很容易地功能化以用作分子载体。这些粒子能够强烈吸收治疗窗中波长的光，并结合表面等离振子共振的加热效果，使其特别适合生物应用中的非侵入性加热。经过特殊设计的DNA适体已显示出它们能够通过插层充当药物载体以及直接充当治疗剂的能力。通过结合这些单独的分子，可以产生具有巨大潜力的多方位药物递送载体，作为癌症的选择性和可控制的治疗方法。使用球形GNP制备了寡核苷酸涂层的GNP，但是用金纳米板以这种方式报道的工作很少。使用Diasynth方法，制备了金纳米板，以在治疗性近红外（nIR）窗口中强烈吸收。这些颗粒用两种DNA寡核苷酸进行了功能化：一种用作阿霉素的插入位点，另一种AS1411直接用作抗癌靶向/治疗剂。这些功能性粒子已完全合成并经过处理，同时确认了DNA功能化和阿霉素嵌入。阿霉素通过DNA结构的变性而释放，当金纳米板被加热到远高于DNA熔化温度时，阿霉素插入该DNA结构中。在激光应用过程中，由于表面等离振子共振的光刺激而导致温度升高。通过荧光测量测量了通过激光施加的阿霉素的成功释放，这提供了成功插入和释放阿霉素的证据。

著录项

  • 作者

    Brann, Tyler.;

  • 作者单位

    University of Louisville.;

  • 授予单位 University of Louisville.;
  • 学科 Biomedical engineering.;Oncology.;Nanotechnology.
  • 学位 M.Eng.
  • 年度 2014
  • 页码 58 p.
  • 总页数 58
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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