An extracellular pH-driven targeted multifunctional manganese arsenite delivery system for tumor imaging and therapy
An extracellular pH-driven targeted multifunctional manganese arsenite delivery system for tumor imaging and therapy
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用于肿瘤成像和治疗的细胞外 pH 驱动的靶向多功能亚砷酸锰输送系统
DOI：
10.1039/c9bm00216b
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发表时间：
2019
影响因子：
6.6
通讯作者：
Shan Hong
中科院分区：
文献类型：
--
作者：
Zhang Ke;Lin Hongyu;Mao Junjie;Luo Xiangjie;Wei Ruixue;Su Zhongzhen;Zhou Bin;Li Dan;Gao Jinhao;Shan Hong
近年来，三氧化二砷（ATO，As 2 O3）在癌症化疗中的扩大使用受到广泛关注，因为其在治疗急性早幼粒细胞白血病（APL）方面效果显着。目前，ATO生物相容性差，毒副作用大，限制了其在实体瘤临床治疗中的应用。为了解决这些局限性，在这里，我们开发了一种pH低插入肽（pHLIP）修饰的ATO为基础的多功能药物传递系统（DDS），这是被称为MnAs@SiO2-pHLIP。通过pHLIP的包被，MnAs@SiO2-pHLIP可以有效靶向酸性肿瘤微环境，导致DDS在细胞内的高积累。作为一种“智能”纳米粒子（NP）平台，DDS能够在酸性环境中可控地释放负载的ATO，促进癌细胞凋亡。与游离ATO相比，ATO的控释能力和突出的靶向能力使其具有更好的抗癌效果和更低的对正常组织的毒性。值得注意的是，酸性肿瘤微环境也会触发锰离子（Mn 2+）的释放，使T1信号变亮，T1信号可通过对比增强磁共振成像（MRI）进行实时监测。体外和体内实验均证明，这些多功能特征可能会扩大ATO在实体瘤治疗中的应用。我们相信MnAs@SiO2-pHLIP可以作为癌症治疗诊断的吉祥剂，并在癌症管理中找到巨大的应用。
Expanding the use of arsenic trioxide (ATO, As2O3) in cancer chemotherapy has received extensive attention in recent years owing to its remarkable efficacy in treating acute promyelocytic leukemia (APL). To date, the use of ATO for clinical treatment of solid tumors is still limited by its poor biocompatibility and severe toxic side effects. To address these limitations, here we developed a pH-low insertion peptide (pHLIP) modified ATO-based multifunctional drug-delivery system (DDS), which is termed MnAs@SiO2–pHLIP. With the coating of pHLIP, MnAs@SiO2–pHLIP could efficiently target the acidic tumor microenvironment, resulting in high intracellular accumulation of the DDS. As a “smart” nanoparticle (NP) platform, the DDS could controllably discharge the loaded ATO in response to acidic environments, which promotes the apoptosis of cancer cells. The features of controlled release capacity and the outstanding targeting ability contribute to better anticancer efficacy and less toxicity towards normal tissues compared with free ATO. It is worth noting that the acidic tumor microenvironment would also trigger the release of manganese ions (Mn2+) that brighten the T1 signal, which is exploited for real-time monitoring via contrast-enhanced magnetic resonance imaging (MRI). These multifunctional features, as demonstrated by both in vitro and in vivo experiments, could potentially expand the use of ATO to the treatment of solid tumors. We believe that MnAs@SiO2–pHLIP could serve as an auspicious agent for cancer theranostics and find tremendous applications in cancer management.