Youngren-Ortiz Susanne R, Chougule Mahavir B
Translational Drug Delivery Research Laboratory (DDR), Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI (SRY-O, MBC).
Hawaii J Med Public Health. 2017 Nov;76(11):318-325.
In Hawai'i, lung cancer is among the top cancers diagnosed and a leading cause of death. Despite current understanding and modern surgery, radiology, and chemotherapy techniques, the survival of those suffering from lung cancer remains low. Current anticancer drugs have poor tumor tissue selectivity and toxicity issues that contribute to their overall low efficacy, detrimental effects to normal tissues, and drug resistance. A potential way of mitigating cancer is through RNA interference (RNAi) by the delivery of small interfering RNA (siRNA) to target select proteins or genes involved in cancer progression, known as oncoproteins or oncogenes, respectively. However, the clinical utility of delivering unformulated siRNA has been hindered due to poor cell penetration, nonspecific effects, rapid degradation, and short half-life. As an alternate for conventional chemotherapy, nanoparticles (AKA nanocarriers) may be designed to localize within the tumor environment and increase targeted cell internalization, thus reducing systemic adverse effects and increasing efficacy. Nanoparticles play important roles in drug delivery and have been widely studied for cancer therapy and diagnostics, termed collectively as theranostics. Nanoparticles composed of natural and artificial polymers, proteins, lipids, metals, and carbon-based materials have been developed for the delivery of siRNA. Cancer targeting has been improved by nanoparticle surface modification or conjugation with biomolecules that are attracted to or stimulate therapeutic agent release within cancer tissues or cells. In this mini-review article, we present recent progress in nanocarrier-mediated siRNA delivery systems that include lipid, polymer, metallic and carbon-based nanoparticles for lung cancer therapy.
在夏威夷，肺癌是诊断出的最常见癌症之一，也是主要死因。尽管有目前的认知以及现代手术、放射学和化疗技术，但肺癌患者的生存率仍然很低。目前的抗癌药物肿瘤组织选择性差且存在毒性问题，导致其总体疗效低、对正常组织有不良影响以及产生耐药性。一种潜在的减轻癌症的方法是通过RNA干扰（RNAi），即递送小干扰RNA（siRNA）来靶向参与癌症进展的特定蛋白质或基因，分别称为癌蛋白或癌基因。然而，由于细胞穿透性差、非特异性效应、快速降解和半衰期短，未配制的siRNA的临床应用受到了阻碍。作为传统化疗的替代方法，可以设计纳米颗粒（也称为纳米载体）使其定位于肿瘤环境中并增加靶向细胞内化，从而减少全身不良反应并提高疗效。纳米颗粒在药物递送中发挥着重要作用，并且已经在癌症治疗和诊断（统称为治疗诊断学）方面得到了广泛研究。由天然和人工聚合物、蛋白质、脂质、金属和碳基材料组成的纳米颗粒已被开发用于递送siRNA。通过纳米颗粒表面修饰或与能在癌症组织或细胞内吸引或刺激治疗剂释放的生物分子结合，癌症靶向性得到了改善。在这篇综述文章中，我们介绍了纳米载体介导的siRNA递送系统的最新进展，这些系统包括用于肺癌治疗的脂质、聚合物、金属和碳基纳米颗粒。
