Zhang Liang, Zhang Zhongwei, Mason Ralph P, Sarkaria Jann N, Zhao Dawen
Radiology, UT Southwestern Medical Center, Dallas, TX.
Radiation Oncology, Mayo Clinic, Rochester, MN.
Sci Rep. 2015 May 12;5:9874. doi: 10.1038/srep09874.
There is considerable interest in developing nanohybrids of imaging contrast agents and drugs for image-guided drug delivery. We have developed a strategy of utilizing manganese (Mn) to enhance the nano-encapsulation of arsenic trioxide (ATO). Formation of arsenite (As(3+))-Mn precipitates in liposomes generates magnetic susceptibility effects, reflected as dark contrast on T2-weighted MRI. Intriguingly, following cell uptake, the As-Mn complex decomposes in response to low pH in endosome-lysosome releasing ionic As(3+), the active form of ATO, and Mn(2+), the T1 contrast agent that gives a bright signal. Glioblastoma (GBM) is well known for its high resistance to chemotherapy, e.g., temozolomide (TMZ). Building upon the previously established phosphatidylserine (PS)-targeted nanoplatform that has excellent GBM-targeting specificity, we now demonstrate the effectiveness of the targeted nanoformulated ATO for treating TMZ-resistant GBM cells and the ability of the convertible Mn contrast as a surrogate revealing the delivery and release of ATO.
开发用于图像引导药物递送的成像造影剂与药物的纳米复合物引起了广泛关注。我们已开发出一种利用锰（Mn）来增强三氧化二砷（ATO）纳米封装的策略。脂质体中亚砷酸盐（As(3+)）-Mn沉淀物的形成会产生磁化率效应，在T2加权磁共振成像（MRI）上表现为暗对比度。有趣的是，细胞摄取后，As-Mn复合物会因内体-溶酶体中的低pH值而分解，释放出离子态As(3+)（ATO的活性形式）和Mn(2+)（产生明亮信号的T1造影剂）。胶质母细胞瘤（GBM）以其对化疗（如替莫唑胺（TMZ））的高度抗性而闻名。基于先前建立的具有优异GBM靶向特异性的磷脂酰丝氨酸（PS）靶向纳米平台，我们现在证明了靶向纳米制剂ATO治疗TMZ抗性GBM细胞的有效性，以及可转换Mn造影剂作为替代物揭示ATO递送和释放的能力。
