Silica nanoparticles have been one of the most promising nanosystems for biomedical applications due to their facile surface chemistry and non-toxic nature. However, it is still challenging to effectively deliver them...Silica nanoparticles have been one of the most promising nanosystems for biomedical applications due to their facile surface chemistry and non-toxic nature. However, it is still challenging to effectively deliver them into tumor sites and noninvasively visualize their in vivo biodistribution with excellent sensitivity and accuracy for effective cancer diagnosis. In this study, we design a yolk/shell-structured silica nanosystem ^(64) Cu-NOTAQD@HMSN-PEG-TRC105, which can be employed for tumor vasculature targeting and dual-modality PET/optical imaging, leading to superior targeting specificity, excellentimaging capability and more reliable diagnostic outcomes.By combining vasculature targeting, pH-sensitive drug delivery, and dual-modality imaging into a single platform,as-designed yolk/shell-structured silica nanosystems may be employed for the future image-guided tumor-targeted drug delivery, to further enable cancer theranostics.展开更多
Objective: Charcot-Marie-Tooth (CMT) neuropathy with visual impairment due to optic atrophy has been designated as hereditary motor and sensory neuropathy type VI (HMSN VI). Reports of affected families have indicated...Objective: Charcot-Marie-Tooth (CMT) neuropathy with visual impairment due to optic atrophy has been designated as hereditary motor and sensory neuropathy type VI (HMSN VI). Reports of affected families have indicated autosomal dominant and recessive forms,but the genetic cause of this disease has remained elusive. Methods:Here,we describe six HMSN VI families with a subacute onset of optic atrophy and subsequent slow recovery of visual acuity in 60% of the patients. Detailed clinical and genetic studies were performed. Results: In each pedigree,we identified a unique mutation in the gene mitofusin 2 (MFN2). In three families,the MFN2 mutation occurred de novo; in two families the mutation was subsequently transmitted from father to son indicating autosomal dominant inheritance. Interpretation: MFN2 is a mitochondrial membrane protein that was recently reported to cause axonal CMT type 2A. It is intriguing that MFN2 shows functional overlap with optic atrophy 1 (OPA1),the protein underlying the most common form of autosomal dominant optic atrophy,and mitochondrial encoded oxidative phosphorylation components as seen in Leber’ s hereditary optic atrophy. We conclude that autosomal dominant HMSN VI is caused by mutations in MFN2,emphasizing the important role of mitochondrial function for both optic atrophies and peripheral neuropathies.展开更多
基金supported,in part,by the University of Wisconsin–Madisonthe National Institutes of Health (P30CA014520 and T32CA009206)the American Cancer Society (125246-RSG-13-099-01-CCE)
文摘Silica nanoparticles have been one of the most promising nanosystems for biomedical applications due to their facile surface chemistry and non-toxic nature. However, it is still challenging to effectively deliver them into tumor sites and noninvasively visualize their in vivo biodistribution with excellent sensitivity and accuracy for effective cancer diagnosis. In this study, we design a yolk/shell-structured silica nanosystem ^(64) Cu-NOTAQD@HMSN-PEG-TRC105, which can be employed for tumor vasculature targeting and dual-modality PET/optical imaging, leading to superior targeting specificity, excellentimaging capability and more reliable diagnostic outcomes.By combining vasculature targeting, pH-sensitive drug delivery, and dual-modality imaging into a single platform,as-designed yolk/shell-structured silica nanosystems may be employed for the future image-guided tumor-targeted drug delivery, to further enable cancer theranostics.
文摘Objective: Charcot-Marie-Tooth (CMT) neuropathy with visual impairment due to optic atrophy has been designated as hereditary motor and sensory neuropathy type VI (HMSN VI). Reports of affected families have indicated autosomal dominant and recessive forms,but the genetic cause of this disease has remained elusive. Methods:Here,we describe six HMSN VI families with a subacute onset of optic atrophy and subsequent slow recovery of visual acuity in 60% of the patients. Detailed clinical and genetic studies were performed. Results: In each pedigree,we identified a unique mutation in the gene mitofusin 2 (MFN2). In three families,the MFN2 mutation occurred de novo; in two families the mutation was subsequently transmitted from father to son indicating autosomal dominant inheritance. Interpretation: MFN2 is a mitochondrial membrane protein that was recently reported to cause axonal CMT type 2A. It is intriguing that MFN2 shows functional overlap with optic atrophy 1 (OPA1),the protein underlying the most common form of autosomal dominant optic atrophy,and mitochondrial encoded oxidative phosphorylation components as seen in Leber’ s hereditary optic atrophy. We conclude that autosomal dominant HMSN VI is caused by mutations in MFN2,emphasizing the important role of mitochondrial function for both optic atrophies and peripheral neuropathies.
