替莫唑胺
胶质母细胞瘤
抗药性
缺氧(环境)
药物输送
肿瘤微环境
药品
活性氧
光热治疗
癌症研究
肿瘤缺氧
化学
药理学
靶向给药
医学
肿瘤细胞
放射治疗
生物
纳米技术
内科学
材料科学
氧气
生物化学
微生物学
有机化学
作者
Xiaojie Chen,Yuyi Zheng,Qi Zhang,Qi Chen,Zhong Chen,Di Wu
标识
DOI:10.1186/s12951-024-02531-3
摘要
Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor with low survival rate. Currently, temozolomide (TMZ) is the first-line drug for GBM treatment of which efficacy is unfortunately hindered by short circulation time and drug resistance associated to hypoxia and redox tumor microenvironment. Herein, a dual-targeted and multi-responsive nanoplatform is developed by loading TMZ in hollow manganese dioxide nanoparticles functionalized by polydopamine and targeting ligands RAP12 for photothermal and receptor-mediated dual-targeted delivery, respectively. After accumulated in GBM tumor site, the nanoplatform could respond to tumor microenvironment and simultaneously release manganese ion (Mn 2+ ), oxygen (O 2 ) and TMZ. The hypoxia alleviation via O 2 production, the redox balance disruption via glutathione consumption and the reactive oxygen species generation, together would down-regulate the expression of O 6 -methylguanine-DNA methyltransferase under TMZ medication, which is considered as the key to drug resistance. These strategies could synergistically alleviate hypoxia microenvironment and overcome TMZ resistance, further enhancing the anti-tumor effect of chemotherapy/chemodynamic therapy against GBM. Additionally, the released Mn 2+ could also be utilized as a magnetic resonance imaging contrast agent for monitoring treatment efficiency. Our study demonstrated that this nanoplatform provides an alternative approach to the challenges including low delivery efficiency and drug resistance of chemotherapeutics, which eventually appears to be a potential avenue in GBM treatment.
科研通智能强力驱动
Strongly Powered by AbleSci AI