The ability to selectively kill cancerous cell populations while leaving healthy cells unaffected is a key goal in anticancer therapeutics. The use of nanoporous silica-based materials as drug-delivery vehicles has recently proven successful, yet production of these materials requires costly and toxic chemicals. Here we use diatom microalgae-derived nanoporous biosilica to deliver chemotherapeutic drugs to cancer cells. The diatom Thalassiosira pseudonana is genetically engineered to display an IgG-binding domain of protein G on the biosilica surface, enabling attachment of cell-targeting antibodies. Neuroblastoma and B-lymphoma cells are selectively targeted and killed by biosilica displaying specific antibodies sorbed with drug-loaded nanoparticles. Treatment with the same biosilica leads to tumour growth regression in a subcutaneous mouse xenograft model of neuroblastoma. These data indicate that genetically engineered biosilica frustules may be used as versatile 'backpacks' for the targeted delivery of poorly water-soluble anticancer drugs to tumour sites.

Biomineral‐forming organisms provide inspiration for developing new reaction pathways to functional materials, such as rutile for optical devices. A recombinant protein (rSilC) was designed based on the sequence of a silica‐forming protein from a diatom. This unique protein induced the formation of hierarchically nanostructured rutile microcrystals under mild reaction conditions (see SEM image).

Background: Morphogenesis of diatom biosilica depends on a silaffin-dependent organic matrix inside intracellular vesicles (SDVs). Results: Silaffin-derived 12-14-mer peptides containing five modified lysines and several phosphoserines (pentalysine clusters) are sufficient for silica targeting in vivo. Conclusion: Pentalysine clusters function as address tags for SDV targeting of silaffins. Significance: Elucidating the molecular mechanisms for biogenesis of mineral-forming vesicles is essential for understanding biomineral morphogenesis.

Living organisms are adept in forming inorganic materials (biominerals) with unique structures and properties that exceed the capabilities of engineered materials. Biomimetic materials syntheses are being developed that aim at replicating the advantageous properties of biominerals in vitro and endow them with additional functionalities. Recently, proof-of-concept was provided for an alternative approach that allows for the production of biomineral-based functional materials in vivo. In this approach, the cellular machinery for the biosynthesis of nano-/micropatterned SiO 2 (silica) structures in diatoms was genetically engineered to incorporate a monomeric, cofactor-independent ("simple") enzyme, HabB, into diatom silica. In the present work, it is demonstrated that this approach is also applicable for enzymes with "complex" activity requirements, including oligomerization, metal ions, organic redox cofactors, and posttranslational modifications. Functional expression of the enzymes ␤-glucuronidase, glucose oxidase, galactose oxidase, and horseradish peroxidase in the diatom Thalassiosira pseudonana was accomplished, and 66 to 78% of the expressed enzymes were stably incorporated into the biosilica. The in vivo incorporated enzymes represent approximately 0.1% (wt/wt) of the diatom biosilica and are stabilized against denaturation and proteolytic degradation. Furthermore, it is demonstrated that the gene construct for in vivo immobilization of glucose oxidase can be utilized as the first negative selection marker for diatom genetic engineering.