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用于温和光热加热增强基因治疗的生物矿化碳酸钙纳米杂化材料。

Biomineralized calcium carbonate nanohybrids for mild photothermal heating-enhanced gene therapy.

机构信息

Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China; Department of Materials Engineering, Taiyuan Institute of Technology, Taiyuan, 030008, China.

Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China.

出版信息

Biomaterials. 2021 Jul;274:120885. doi: 10.1016/j.biomaterials.2021.120885. Epub 2021 May 13.

DOI:10.1016/j.biomaterials.2021.120885
PMID:34022740
Abstract

It is of great significance to develop multifunctional gene carriers to achieve treatments with enhanced therapeutic effects in an inflammation-free manner. In this work, assembled micelles of polysaccharide were utilized for the biomineralization of calcium carbonate to produce one-dimensional Alg-CaCO nanoparticles. In order to introduce both functions of mild hyperthermia and gene transfection, polydopamine (PDA) coating was applied to conjugate cationic polymers on the surface of nanoparticles. The resultant ACDP nanohybrids exhibited enhanced performance as gene carriers under near infrared (NIR) light irradiation at a low power density. Meanwhile, the pH-responsive degradation of gene carriers could further promote gene release for better effectiveness. The enhanced gene therapy induces tumor cell apoptosis, which could prevent inflammatory responses. The feasibility of mild hyperthermia-enhanced gene therapy for tumor treatment was investigated in vitro and in vivo. In addition, dual-modal ultrasound (US) and photoacoustic (PA) imaging was also realized to monitor and guide the treatment processes. The current work provides a new avenue for the construction of multifunctional platform to realize cancer therapy with improved therapeutic effectiveness in an inflammation-free manner.

摘要

开发多功能基因载体对于实现无炎症的增强治疗效果具有重要意义。在这项工作中,利用多糖组装胶束进行碳酸钙的生物矿化,以制备一维 Alg-CaCO3 纳米粒子。为了同时引入温和热疗和基因转染两种功能,在纳米粒子表面涂覆聚多巴胺 (PDA) 以连接阳离子聚合物。在低功率密度近红外 (NIR) 光照射下,所得的 ACDP 纳米杂化物作为基因载体表现出增强的性能。同时,基因载体的 pH 响应性降解可以进一步促进基因释放,从而提高疗效。增强的基因治疗诱导肿瘤细胞凋亡,从而防止炎症反应。在体外和体内研究了温和热疗增强的基因治疗用于肿瘤治疗的可行性。此外,还实现了双模态超声 (US) 和光声 (PA) 成像,以监测和指导治疗过程。本工作为构建多功能平台以实现无炎症的增强治疗效果的癌症治疗提供了新途径。

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