Medical applications of nanotechnology typically focus on drug delivery and biosensors. Here, we combine nanotechnology and bioengineering to demonstrate that nanoparticles can be used to remotely regulate protein production in vivo. We decorated a modified temperature-sensitive channel, TRPV1, with antibody-coated iron oxide nanoparticles that are heated in a low-frequency magnetic field. When local temperature rises, TRPV1 gates calcium to stimulate synthesis and release of bioengineered insulin driven by a Ca2+-sensitive promoter. Studying tumor xenografts expressing the bioengineered insulin gene, we show that exposure to radio waves stimulates insulin release from the tumors and lowers blood glucose in mice. We further show that cells can be engineered to synthesize genetically encoded ferritin nanoparticles and inducibly release insulin. These approaches provide a platform for using nanotechnology to activate cells.

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Biomaterials produced by nature have been honed through billions of years, evolving exquisitely precise structure-function relationships that scientists strive to emulate. Advances in genetic engineering have facilitated extensive investigations to determine how changes in even a single peptide within a protein sequence can produce biomaterials with unique thermal, mechanical and biological properties. Elastin, a naturally occurring protein polymer, serves as a model protein to determine the relationship between specific structural elements and desirable material characteristics. The modular, repetitive nature of the protein facilitates the formation of well-defined secondary structures with the ability to self-assemble into complex three-dimensional architectures on a variety of length scales. Furthermore, many opportunities exist to incorporate other protein-based motifs and inorganic materials into recombinant protein-based materials, extending the range and usefulness of these materials in potential biomedical applications. Elastin-like polypeptides can be assembled into 3D architectures with precise control over payload encapsulation, mechanical and thermal properties, as well as unique functionalization opportunities through both genetic and enzymatic means. An overview of current protein-based materials, their properties and uses in biomedicine will be provided, with a focus on the advantages of elastin-like polypeptides. Applications of these biomaterials as imaging and therapeutic delivery agents will be discussed. Finally, broader implications and future directions of these materials as diagnostic and therapeutic systems will be explored.

The promise of nanobiomaterials for diagnostic and therapeutic biomedical applications has been widely reported throughout the scientific community, and great strides have been made in those directions. And yet, the translation of nanomaterial-based therapeutics to clinical applications remains an elusive target. Many challenges have blocked the usage of nanomaterials in biomedicine, including potential toxicity, immunogenicity, and decreased efficacy. In order to overcome some of these issues, detailed studies have been undertaken to understand fundamental interactions between nanomaterials and the biological environment. In particular, recent developments in nanoparticle synthesis, a better understanding and control over nanoparticle surface chemistry, as well as the organization of that chemistry on the nanoparticle surface, has allowed researchers to begin to understand how spatial arrangement of atomic and molecular species at an interface can affect protein adsorption, structure, and subsequent biological outcomes. This perspective strives to identify ways in which the nanomaterial interface can be controlled to affect interactions with biomolecules for beneficial biomedical applications.