ABSTRACT
BACKGROUND: Biallelic ZBTB11 variants have previously been associated with an ultrarare subtype of autosomal recessive intellectual developmental disorder (MRT69). OBJECTIVE: The aim was to provide insights into the clinical and genetic characteristics of ZBTB11-related disorders (ZBTB11-RD), with a particular emphasis on progressive complex movement abnormalities. METHODS: Thirteen new and 16 previously reported affected individuals, ranging in age from 2 to 50 years, with biallelic ZBTB11 variants underwent clinical and genetic characterization. RESULTS: All patients exhibited a range of neurodevelopmental phenotypes with varying severity, encompassing ocular and neurological features. Eleven new patients presented with complex abnormal movements, including ataxia, dystonia, myoclonus, stereotypies, and tremor, and 7 new patients exhibited cataracts. Deep brain stimulation was successful in treating 1 patient with generalized progressive dystonia. Our analysis revealed 13 novel variants. CONCLUSIONS: This study provides additional insights into the clinical features and spectrum of ZBTB11-RD, highlighting the progressive nature of movement abnormalities in the background of neurodevelopmental phenotype. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
ABSTRACT
Cancer therapy necessitates the development of novel and effective treatment modalities to combat the complexity of this disease. In this project, we propose a synergistic approach by combining chemo-photothermal treatment using gold nanorods (AuNRs) supported on thiol-functionalized mesoporous silica, offering a promising solution for enhanced lung cancer therapy. To begin, mesoporous MCM-41 was synthesized using a surfactant-templated sol-gel method, chosen for its desirable porous structure, excellent biocompatibility, and non-toxic properties. Further, thiol-functionalized MCM-41 was achieved through a simple grafting process, enabling the subsequent synthesis of AuNRs supported on thiol-functionalized MCM-41 (AuNR@S-MCM-41) via a gold-thiol interaction. The nanocomposite was then loaded with the anticancer drug doxorubicin (DOX), resulting in AuNR@S-MCM-41-DOX. Remarkably, the nanocomposite exhibited pH/NIR dual-responsive drug release behaviors, facilitating targeted drug delivery. In addition, it demonstrated exceptional biocompatibility and efficient internalization into A549 lung cancer cells. Notably, the combined photothermal-chemo therapy by AuNR@S-MCM-41-DOX exhibited superior efficacy in killing cancer cells compared to single chemo- or photothermal therapies. This study showcases the potential of the AuNR@S-MCM-41-DOX nanocomposite as a promising candidate for combined chemo-photothermal therapy in lung cancer treatment. The innovative integration of gold nanorods, thiol-functionalized mesoporous silica, and pH/NIR dual-responsive drug release provides a comprehensive and effective therapeutic approach for improved outcomes in lung cancer therapy. Future advancements based on this strategy hold promise for addressing the challenges posed by cancer and transforming patient care.