AUTHOR=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 

TITLE=Intelligent Nanoparticles With pH-Sensitive Co-Delivery of Temozolomide and siEGFR to Ameliorate Glioma Therapy

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.921051

DOI=10.3389/fgene.2022.921051

ISSN=1664-8021

ABSTRACT=The glioblastoma (GBM) is one of the most lethal forms of human cancer, with very few long-term survivors. Besides 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 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 is a huge advantage. In this paper, pH-sensitive as well as GBM-targeting nanovesicle (Tf-PEG-PAE(SS)) was fabricated. Chemotherapy drug (TMZ) and EGFR inhibitor (siEGFR) were co-encapsulated in the nanocarrier and their anticancer outcome were investigated in detail. In vitro experiments have shown that the nanocarrier transports TMZ and siEGFR efficiently into U87 cells, causing a vigorous apoptotic response by silencing 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 intracranial injection of Tf-PEG-PAE(SS)/TMZ@siEGFR. The drug co-delivery system could extend the blood circulation time by escaping immune clearance, which offer a new strategy to treat glioblastoma.