Many biological mechanisms including cellular metabolism and cell death are regulated by mitochondria known as powerhouse of the cell. Recently, let-7b, a tumour-suppressor microRNA has been detected in mitochondria of human cells targeting several mitochondrial-encoded respiratory chain genes. Triphenylphosphonium cation (TPP) is one of the major classes of mitochondriotropics that possess the ability of specifically targeting the mitochondria. PAMAM dendrimers are one of the most available agents in gene delivery due to their well-defined and beneficial features such as large density of surface functional groups. Hyaluronic acid (HA), a natural polysaccharide has been demonstrated to have the abilities such as good biocompatibility and targeting CD44 overexpressed receptors on non-small cell lung cancer (NSCLC) cells. In this research, let-7b-PAMAM (G5)-TPP and let-7b-PAMAM (G5)-TPP-HA nano-carriers were designed to deliver let-7b miRNA mimic to NSCLC cells’ mitochondria as a novel way of cancer cells inhibition. Nano-carriers were capable of being successfully taken up by A549 cells and localised in mitochondria environment. Let-7b loaded nanoparticles reduced cell viability and induced apoptosis significantly. Expression of genes involved in mitochondrial oxidative function was decreased resulting in nanoparticles effect on mitochondria. Application of mitochondria targeted-miRNA delivery systems could regulate cellular functions to inhibit lung cancer.

许多生物机制，包括细胞代谢和细胞死亡，都由被称为细胞动力的线粒体调节。最近，在人类细胞的线粒体中检测到了一种肿瘤抑制因子 microRNA let-7b，靶向几个线粒体编码的呼吸链基因。三苯基鏻阳离子 (TPP) 是具有特异性靶向线粒体的能力的主要线粒体药物类别之一。PAMAM 树枝状聚合物是基因传递中最可用的试剂之一，因为它们具有明确且有益的特征，例如大密度的表面官能团。透明质酸 (HA) 是一种天然多糖，已被证明具有良好的生物相容性和靶向非小细胞肺癌 (NSCLC) 细胞上过表达的 CD44 受体等能力。在这项研究中，let-7b-PAMAM (G5)-TPP 和 let-7b-PAMAM (G5)-TPP-HA 纳米载体旨在将 let-7b miRNA 模拟物递送至 NSCLC 细胞的线粒体，作为一种新型抑制癌细胞的方法。纳米载体能够被 A549 细胞成功吸收并定位在线粒体环境中。加载 Let-7b 的纳米颗粒显着降低细胞活力并诱导细胞凋亡。参与线粒体氧化功能的基因表达降低，导致纳米颗粒对线粒体的影响。线粒体靶向miRNA递送系统的应用可以调节细胞功能以抑制肺癌。纳米载体能够被 A549 细胞成功吸收并定位在线粒体环境中。加载 Let-7b 的纳米颗粒显着降低细胞活力并诱导细胞凋亡。参与线粒体氧化功能的基因表达降低，导致纳米颗粒对线粒体的影响。线粒体靶向miRNA递送系统的应用可以调节细胞功能以抑制肺癌。纳米载体能够被 A549 细胞成功吸收并定位在线粒体环境中。加载 Let-7b 的纳米颗粒显着降低细胞活力并诱导细胞凋亡。参与线粒体氧化功能的基因表达降低，导致纳米颗粒对线粒体的影响。线粒体靶向miRNA递送系统的应用可以调节细胞功能以抑制肺癌。