Wang Zhen, Liu Yuyang, Xiao Yong, Xie Yandong, Wang Ran, Zhang Yiding, Zhou Qi, Liu Liang, Sun Shuo, Xiao Hong, Zou Yuanjie, Yang Kun, Li Xiang, Zhao Mengjie, Hu Yifang, Liu Hongyi
Department of Neurosurgery, The Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, China.
Department of Neuro-Psychiatric Institute, The Affiliated Brain Hospital with Nanjing Medical University, Nanjing, China.
Front Genet. 2022 Jul 12;13:921051. doi: 10.3389/fgene.2022.921051. eCollection 2022.
Glioblastoma (GBM) is one of the most lethal forms of human cancer, with very few long-term survivors. In addition to surgery, chemotherapy is still an important strategy. Unfortunately, GBM chemotherapy faces two main challenges: first, in GBM, epidermal growth factor receptor (EGFR) overexpression results in chemoresistance; second, temozolomide (TMZ) lacks target specificity, which can lead to a reduction in the concentration and side effects in GBM. Nowadays, with the development of nanomedicine systems for applications in tumor therapies, increasing anticancer efficacy and reducing side effects with multi-drug delivery are huge advantages. In this study, pH-sensitive and GBM-targeting nanovesicle (Tf-PEG-PAE(SS)) was fabricated. The chemotherapy drug (TMZ) and EGFR inhibitor (EGFR-siRNA) were co-encapsulated in the nanocarrier, and their anticancer outcomes were investigated in detail. experiments have shown that the nanocarrier transports TMZ and EGFR-siRNA efficiently into U87 cells, causing a vigorous apoptotic response by silencing the proliferative EGFR gene and increasing the drug concentration of TMZ simultaneously. An experimental study in mice bearing orthotropic glioma revealed that the accumulated nanocarriers in the tumor site could inhibit the tumor growth and prolong the mice survival remarkably through the intracranial injection of Tf-PEG-PAE(SS)/TMZ@siEGFR. The drug co-delivery system could extend the blood circulation time and offer a new strategy to treat glioblastoma.
胶质母细胞瘤（GBM）是人类癌症中最致命的形式之一，长期存活者极少。除手术外，化疗仍是一种重要的治疗策略。不幸的是，GBM化疗面临两个主要挑战：其一，在GBM中，表皮生长因子受体（EGFR）的过度表达导致化疗耐药；其二，替莫唑胺（TMZ）缺乏靶向特异性，这可能导致其在GBM中的浓度降低以及副作用。如今，随着用于肿瘤治疗的纳米药物系统的发展，通过多药递送提高抗癌疗效并减少副作用具有巨大优势。在本研究中，制备了pH敏感且靶向GBM的纳米囊泡（Tf-PEG-PAE(SS)）。将化疗药物（TMZ）和EGFR抑制剂（EGFR-siRNA）共包封于纳米载体中，并详细研究了它们的抗癌效果。实验表明，该纳米载体能将TMZ和EGFR-siRNA有效地转运至U87细胞中，通过沉默增殖性EGFR基因并同时提高TMZ的药物浓度，引发强烈的凋亡反应。一项对原位胶质瘤小鼠的实验研究表明，通过颅内注射Tf-PEG-PAE(SS)/TMZ@siEGFR，纳米载体在肿瘤部位的蓄积可显著抑制肿瘤生长并延长小鼠生存期。该药物共递送系统可延长血液循环时间，并为治疗胶质母细胞瘤提供一种新策略。
