Silica/organosilica cross-linked block copolymer micelles: a versatile theranostic platform

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.