Lab of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
Chem Soc Rev. 2017 Feb 6;46(3):569-585. doi: 10.1039/c6cs00495d.
As a member of the organic-inorganic hybrid family, silica/organosilica cross-linked block copolymer micelles are becoming increasingly attractive due to the combined features of excellent self-assembly properties of amphiphilic block copolymers and the high stability and the easy surface modification of silica/organosilica components. Compared to the traditional cross-linking route with organic components, the silica/organosilica cross-linking approach could offer more advantages, such as quick reaction under mild conditions, a much stronger barrier to the diffusion of both encapsulated small molecules and functional nanoparticles and the substantial improvement in the stability of the whole micelles against the ambient environment. In this tutorial review, we will focus on the recent developments in the design, synthesis and biomedical applications of silica/organosilica cross-linked block copolymer micelles based on the self-assembly of amphiphilic block copolymers and the hydrolysis and condensation of silanes in aqueous solution. First, we will summarize the synthesis of three typical kinds of silica/organosilica cross-linked block copolymer micelles based on the self-assembly of non-ionic polyethylene oxide (PEO)-based, cationic and anionic poly(acrylic acid) (PAA)-based block copolymer micelles. Then, a series of multifunctional silica/organosilica cross-linked block copolymer micelles by encapsulating various functional nanoparticles/molecules in the hydrophobic polymer cores or hydrophilic silica/organosilica cross-linked shells are introduced and their biomedical applications in controlled drug delivery, bio-imaging (magnetic resonance, fluorescence and multimodal imaging) and imaging-guided therapies (photothermal and high intensity focused ultrasound therapies) will be discussed. Finally, the challenges and prospects of silica/organosilica cross-linked micellar nanostructures and their biological applications are discussed and assessed. It is highly expected that the silica/organosilica cross-linked micelles may provide a new and promising kind of carrier system for enhanced bio-imaging and efficient cancer therapy.
作为有机-无机杂化家族的一员，由于两亲嵌段共聚物优异的自组装性能与硅烷/有机硅组分的高稳定性和易于表面修饰的结合，硅烷/有机硅交联嵌段共聚物胶束越来越受到关注。与传统的含碳交联路线相比，硅烷/有机硅交联方法具有许多优势，例如在温和条件下快速反应、对包封的小分子和功能纳米颗粒的扩散具有更强的阻挡作用以及对整个胶束在环境中的稳定性有显著提高。在本综述中，我们将重点介绍基于两亲嵌段共聚物自组装和硅烷在水溶液中的水解缩合设计、合成和生物医学应用的硅烷/有机硅交联嵌段共聚物胶束的最新进展。首先，我们将总结三种基于非离子聚环氧乙烷（PEO）基、阳离子和阴离子聚丙烯酸（PAA）基嵌段共聚物胶束自组装的典型硅烷/有机硅交联嵌段共聚物胶束的合成。然后，介绍了一系列通过将各种功能纳米颗粒/分子包封在疏水性聚合物核或亲水性硅烷/有机硅交联壳中制备的多功能硅烷/有机硅交联嵌段共聚物胶束，并讨论了它们在控制药物输送、生物成像（磁共振、荧光和多模态成像）和成像引导治疗（光热和高强度聚焦超声治疗）中的生物医学应用。最后，讨论和评估了硅烷/有机硅交联胶束纳米结构及其生物应用的挑战和前景。有望为增强生物成像和高效癌症治疗提供一种新的有前途的载体系统。
