Smart MSN-Drug-Delivery System for Tumor Cell Targeting and Tumor Microenvironment Release.

Tumor-targeted delivery and controlled release of antitumor drugs are promising strategies for increasing chemotherapeutic efficacy and reducing adverse effects. Although mesoporous silica nanoparticles (MSNs) have been known as a potential delivery system for doxorubicin (DOX), they have restricted applications due to their uncontrolled leakage and burst release from their large open pores. Herein, we engineered a smart drug-delivery system (smart MSN-drug) based on MSN-drug loading, cell membrane mimetic coating, on-demand pore blocking/opening, and tumor cell targeting strategies. The pore size of DOX-loaded MSNs was narrowed by polydopamine coating, and the pores/channels were blocked with tumor-targeting ligands anchored by tumor environment-rupturable -SS- chains. Furthermore, a cell membrane mimetic surface was constructed to enhance biocompatibility of the smart MSN-drug. Confocal microscopy results demonstrate highly selective uptake (12-fold in comparison with L929 cell) of the smart MSN-drug by HeLa cells and delivery into the HeLa cellular nuclei. Further in vitro IC50 studies showed that the toxicity of the smart MSN-drug to HeLa cells was 4000-fold higher than to the normal fibroblast cells. These exciting results demonstrate the utility of the smart MSN-drug capable of selectively killing tumor cells and saving the normal cells.

Apolipoprotein E ε4: A Possible Risk Factor of Intracranial Pressure and White Matter Perfusion in Good-Grade Aneurysmal Subarachnoid Hemorrhage Patients at Early Stage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating and complicated disease with significant morbidity and mortality. Previous studies have shown that genetic susceptibility may play an important role in the outcome of a given individual with aSAH. This study evaluates the potential association in effects of the APOE allele on the early brain injury (EBI) in light of elevated intracranial pressure (ICP) and cerebral perfusion disorders in a consecutive series of non-comatose Chinese patients with aSAH. A total of 122 patients with aSAH (54 males and 68 females) were enrolled in this study. Demographic and clinical data were collected. We measured ICP before microsurgical clipping or endovascular coiling during the first 72 h after aneurysm rupture. Computed tomography perfusion (CTP) examination in patients was performed before treatment. The distributions of APOE genotypes and alleles matched Hardy-Weinberg law (p > 0.05). In this study, 68 patients (55.7%) had a normal ICP, whereas 54 (44.3%) had an elevated ICP. Fourteen of 21 patients with APOE ε4 had an elevated ICP, which was significantly different from those without APOE ε4 (p = 0.03). The patients with the ε4 allele had a higher incidence of elevated ICP [p = 0.009, 95% confidence interval (CI) = 1.481-15.432, odds ratio = 4.780] than those without this allele. For CTP measurements, a lower mean cerebral blood flow (difference, -4.74; 95% CI, 0.53-8.94 s, p = 0.03), longer mean transit time (difference, 0.47; 95% CI, -0.87 to -0.78, p = 0.02), and time-to-peak (difference, 2.29; 95% CI, -3.64 to -0.93 s, p = 0.02) were observed in patients with ε4 allele than in those without in the internal capsule regions. In conclusion, the APOE ε4 allele predisposes patients to elevated ICP and perfusion disorders in white matter regions during the first 72 h after aSAH. The presence of an APOE ε4 allele plays an important role in the EBI response to aSAH.