Signal amplification based on biofunctional nanomaterials has recently attracted considerable attention due to the need for ultrasensitive bioassays and the trend towards miniaturized assays. The biofunctional nanomaterials can not only produce a synergic effect among catalytic activity, conductivity and biocompatibility to accelerate the signal transduction, but also provide amplified recognition events by high loading of signal tags, leading to a highly sensitive and specific biosensing. Most importantly, nanoscaled materials are in direct contact with the environment, which permits them to act as chemical and biological sensors in single-molecule detection of biomolecules. In this tutorial review, we will focus on recent significant advances in signal amplification strategies combining the cross-disciplines of chemistry, biology, and materials science, and highlight some elegant applications of biofunctional nanomaterials as excellent electronic or optical signal tags in ultrasensitive bioanalysis. The biofunctional nanomaterials-based biosensing opens a series of concepts for basic research and offers new tools for detection of trace amounts of a wide variety of analytes in clinical, environmental, and industrial applications.

Metal–organic frameworks (MOFs) are an emerging class of molecular crystalline materials built from metal ions or clusters bridged by organic linkers. By taking advantage of their synthetic tunability and structural regularity, MOFs can hierarchically integrate nanoparticles and/or biomolecules into a single framework to enable multifunctions. The MOF-protected heterostructures not only enhance the catalytic capacity of nanoparticle components but also retain the biological activity of biomolecules in an intracellular microenvironment. Therefore, the multifunctional MOF heterostructures have great advantages over single components in cancer therapy. In this review, we comprehensively summarize the general principle of the design and functional modulation of nanoscaled MOF heterostructures, and biomedical applications in enhanced therapy within the last five years. The functions of MOF heterostructures with a controlled size can be regulated by designing various functional ligands and in situ growth/postmodification of nanoparticles and/or biomolecules. The advances in the application of multifunctional MOF heterostructures are also explored for enhanced cancer therapies involving photodynamic therapy, photothermal therapy, chemotherapy, radiotherapy, immunotherapy, and theranostics. The remaining challenges and future opportunities in this field, in terms of precisely localized assembly, maximizing composite properties, and processing new techniques, are also presented. The introduction of multiple components into one crystalline MOF provides a promising approach to design all-in-one theranostics in clinical treatments.