Roy Bornika, Ghose Sampa, Biswas Subhrajit
Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University, Noida, Uttar Pradesh 201313, India.
Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India.
Semin Cell Dev Biol. 2022 Apr;124:134-144. doi: 10.1016/j.semcdb.2021.04.006. Epub 2021 Apr 26.
Malignancies of hepatocellular carcinoma (HCC) are rapidly spreading and commonly fatal. Like most cancers, the gene expression patterns in HCC vary significantly from patient to patient. Moreover, the expression networks during HCC progression are largely controlled by microRNAs (miRNAs) regulating multiple oncogenes and tumor supressors. Therefore, miRNA-based therapeutic strategies altering these networks may significantly influence the cellular behavior enough for them to cure HCC. However, the most substantial challenges in developing such therapies are the stability of the oligos themselves and that of their delivery systems. Here we provide a comprehensive update describing various miRNA delivery systems, including virus-based delivery and non-viral delivery. The latter may be achieved using inorganic nanoparticles, polymer based nano-carriers, lipid-based vesicles, exosomes, and liposomes. Leaky vasculature in HCC-afflicted livers helps untargeted nanocarriers to accumulate in the tumor tissue but may result in side effects during higher dose of treatment. On the other hand, the strategies for actively targeting miRNA therepeutics to cancerous cells through nano-conjugates or vesicles by decorating their surface with antibodies against or ligands for HCC-specific antigens or receptors are more efficient in preventing damage to healthy tissue and cancer recurrence.
肝细胞癌（HCC）恶性肿瘤正在迅速扩散，通常会导致死亡。与大多数癌症一样，HCC患者的基因表达模式差异很大。此外，HCC进展过程中的表达网络很大程度上受调控多个癌基因和肿瘤抑制因子的微小RNA（miRNA）控制。因此，基于miRNA改变这些网络的治疗策略可能会显著影响细胞行为，足以治愈HCC。然而，开发此类疗法面临的最大挑战是寡核苷酸本身及其递送系统的稳定性。在这里，我们提供了一份全面的最新情况，描述了各种miRNA递送系统，包括基于病毒的递送和非病毒递送。后者可以通过使用无机纳米颗粒、基于聚合物的纳米载体、基于脂质的囊泡、外泌体和脂质体来实现。受HCC影响的肝脏中渗漏的血管有助于非靶向纳米载体在肿瘤组织中积累，但在高剂量治疗期间可能会导致副作用。另一方面，通过用针对HCC特异性抗原或受体的抗体或配体修饰纳米缀合物或囊泡的表面，将miRNA治疗剂主动靶向癌细胞的策略在预防对健康组织的损害和癌症复发方面更有效。
