Top-down fabrication of shape-controlled, monodisperse nanoparticles for biomedical applications

Nanoparticles for biomedical applications are generally formed by bottom-up approaches such as self-assembly, emulsification and precipitation. But these methods usually have critical limitations in fabrication of nanoparticles with controllable morphologies and monodispersed size. Compared with bottom-up methods, top-down nanofabrication techniques offer advantages of high fidelity and high controllability. This review focuses on top-down nanofabrication techniques for engineering particles along with their biomedical applications. We present several commonly used top-down nanofabrication techniques that have the potential to fabricate nanoparticles, including photolithography, interference lithography, electron beam lithography, mold-based lithography (nanoimprint lithography and soft lithography), nanostencil lithography, and nanosphere lithography. Varieties of current and emerging applications are also covered: (i) targeting, (ii) drug and gene delivery, (iii) imaging, and (iv) therapy. Finally, a future perspective of the nanoparticles fabricated by the top-down techniques in biomedicine is also addressed.