Abstract
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.
Highlights
The ability to selectively kill cancerous cell populations while leaving healthy cells unaffected is a key goal in anticancer therapeutics
We have aimed to develop a generic method for the simultaneous attachment of both antibodies and hydrophobic drug molecules to diatom biosilica, without the use of organic solvents and covalent cross-linking
Having characterized the immunoglobulin G (IgG)-binding specificity and capacity of GB1–biosilica, we investigated its function in biological systems
Summary
The ability to selectively kill cancerous cell populations while leaving healthy cells unaffected is a key goal in anticancer therapeutics. Chemical functionalization allows for the tailoring of drug binding and release properties[10,11], and for the covalent immobilization of functional antibody molecules to diatom silica[12,13] Combining both antibody attachment and drug loading on the same diatom silica particle should allow for targeted delivery of the drug to specific locations in vivo, for example, to cancer cells. To achieve (b), we use an established method to encapsulate hydrophobic drug molecules into cationic micelles and liposomes[20,21], followed by investigations on their biosilica-binding properties and the release of the drug molecules This two-step strategy is necessary, as loading of the diatom frustules with a hydrophobic drug from an organic solvent would denature the antibody. This approach leads to multistage drug-delivery vehicles[19,20], where drug-loaded nanoscale vehicles can be deployed once the biosilica has attached to tumour cells (Fig. 1)[20,21]
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