Ferritin Nanocarrier Traverses the Blood Brain Barrier and Kills Glioma. Fan Kelong,Jia Xiaohua,Zhou Meng,Wang Kun,Conde João,He Jiuyang,Tian Jie,Yan Xiyun ACS nano Over the last decades, considerable efforts have been put into developing active nanocarrier systems that cross the blood brain barrier (BBB) to treat brain-related diseases such as glioma tumors. However, to date none have been approved for clinical usage. Here, we show that a human H-ferritin (HFn) nanocarrier both successfully crosses the BBB and kills glioma tumor cells. Its principle point of entry is the HFn receptor (transferrin receptor 1), which is overexpressed in both BBB endothelial cells (ECs) and glioma cells. Importantly, we found that HFn enters and exits the BBB via the endosome compartment. In contrast, upon specifically targeting and entering glioma cells, nearly all of the HFn accumulated in the lysosomal compartment, resulting in the killing of glioma tumor cells, with no HFn accumulation in the surrounding healthy brain tissue. Thus, HFn is an ideal nanocarrier for glioma therapy and possesses the potential to serve as a therapeutic approach against a broad range of central nervous system diseases. 10.1021/acsnano.7b06969

Natural Brain Penetration Enhancer-Modified Albumin Nanoparticles for Glioma Targeting Delivery. Liang Jianming,Gao Caifang,Zhu Ying,Ling Chengli,Wang Qi,Huang Yongzhuo,Qin Jing,Wang Jue,Lu Weigen,Wang Jianxin ACS applied materials & interfaces The unsatisfactory therapeutic outcome for glioma is mainly due to the poor blood-brain barrier (BBB) permeability and inefficient accumulation in the glioma area of chemotherapeutic agents. The existing drug delivery strategies can increase drug transport to the brain but are restricted by side effects and/or poor delivery efficiency. In this study, potent brain penetration enhancers were screened from the active components of aromatic resuscitation drugs used in traditional Chinese medicine. A novel glioma-targeting system based on enhancer-modified albumin nanoparticles was developed to safely and efficiently deliver drugs to the glioma regions in the brain. The nanoparticles improved the transport of nanoparticles across brain capillary endothelial cell (BCEC) monolayer by increasing endocytosis in endothelial cells and causing BBB disruption. In vivo imaging studies demonstrated that the systems could enter the brain and subsequently accumulate in glioma cells with a much higher targeting efficiency than that of transferrin-modified albumin nanoparticles. Of note, the nanoparticles could be captured and penetrate through endothelial cells fenestrae in pineal gland, which is suggestive of an effective way to deliver a nanosystem to the brain by bypassing the BBB. The nanoparticles showed good biocompatibility and negligible cytotoxicity. The results reveal an efficient and safe strategy for brain drug delivery in glioma therapy. 10.1021/acsami.8b11782