ABSTRACT
The strategy of in vivo self-assembly has been developed for improved enrichment and long-term retention of anticancer drug in tumor tissues. However, most self-assemblies with non-covalent bonding interactions are susceptible to complex physiological environments, leading to weak stability and loss of biological function. Here, we develop a coupling-induced assembly (CIA) strategy to generate covalently crosslinked nanofibers, which is applied for in situ constructing artificial shell on mitochondria. The oxidation-responsive peptide-porphyrin conjugate P1 is synthesized, which self-assemble into nanoparticles. Under the oxidative microenvironment of mitochondria, the coupling of thiols in P1 causes the formation of dimers, which is further ordered and stacked into crosslinked nanofibers. As a result, the artificial shell is constructed on the mitochondria efficiently through multivalent cooperative interactions due to the increased binding sites. Under ultrasound (US) irradiation, the porphyrin molecules in the shell produce a large amount of reactive oxygen species (ROS) that act on the adjacent mitochondrial membrane, exhibiting ~2-fold higher antitumor activity than nanoparticles in vitro and in vivo. Therefore, the mitochondria-targeted CIA strategy provides a novel perspective on improved sonodynamic therapy (SDT) and shows potential applications in antitumor therapies.
ABSTRACT
INTRODUCTION: Treatment of complex anterior circulation aneurysms with flow diverters (FDs) has become common practice in neurovascular centers. However, this treatment method for posterior circulation aneurysms (PCAs) still remains controversial. METHODS: Through searches for reports on the treatment of PCAs with FDs, we conducted a systematic review of the literature on its clinical efficacy and safety using random-effect binomial meta-analysis. RESULTS: We included 14 studies, which reported on a total of 225 PCAs in 220 patients. Procedure-related good outcome rate was 79% (95% confidence interval (CI), 72-84), with significantly lower odds among patients with ruptured aneurysms and basilar artery aneurysms. Procedure-related mortality rate was 15% (95% CI 10-21), with significantly higher rates among patients with giant aneurysms and basilar artery aneurysms. The rate of complete aneurysm occlusion at 6-month digital subtraction angiography (DSA) was 84%. Ischemic stroke rate was 11%. Perforator infarction rate was 7%. Postoperative subarachnoid hemorrhage (SAH) rate was 3%. Intraparenchymal hemorrhage (IPH) rate was 4%. CONCLUSIONS: Flow diverter treatment of PCAs is an effective method, which provides a high rate of complete occlusion at 6-month DSA. However, compared with anterior circulation aneurysms, patients with PCAs are at significantly higher risk of mortality, ischemic stroke and perforator infarction. Our findings indicate that, in most clinical centers, flow diverter treatment of PCAs should be conducted in carefully selected patients with poor natural history and no optimal treatment strategy. For ruptured and giant basilar artery aneurysms, there is still no good treatment option.