title: Targeted drug delivery using genetically engineered diatom biosilica.
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.
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Future Industries Institute, University of South Australia, Mawson Lakes Boulevard, Mawson Lakes, South Australia 5095, Australia.
authors.forename: Bahman
authors.initials: B
authors.lastname: Delalat
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
authors.forename: Vonda C
authors.initials: VC
authors.lastname: Sheppard
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Future Industries Institute, University of South Australia, Mawson Lakes Boulevard, Mawson Lakes, South Australia 5095, Australia.
authors.forename: Soraya
authors.initials: S
authors.lastname: Rasi Ghaemi
authors.affiliation: School of Pharmacy and Medical Sciences , University of South Australia, Adelaide, South Australia 5001, Australia.
authors.forename: Shasha
authors.initials: S
authors.lastname: Rao
authors.affiliation: School of Pharmacy and Medical Sciences , University of South Australia, Adelaide, South Australia 5001, Australia.
authors.forename: Clive A
authors.initials: CA
authors.lastname: Prestidge
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Future Industries Institute, University of South Australia, Mawson Lakes Boulevard, Mawson Lakes, South Australia 5095, Australia.
authors.forename: Gordon
authors.initials: G
authors.lastname: McPhee
authors.affiliation: Department of Human Physiology, Centre for Neuroscience, Flinders University, Adelaide, South Australia 5001, Australia.
authors.forename: Mary-Louise
authors.initials: ML
authors.lastname: Rogers
authors.affiliation: Oncogenic Signalling Laboratory and Brain Cancer Discovery Collaborative, Centre for Cancer Research, Hudson Institute of Medical Research, Wright Street, Clayton, Victoria 3168, Australia.|Monash University, Wellington Parade, Clayton, Victoria 3168, Australia.
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: Donoghue
authors.affiliation: Oncogenic Signalling Laboratory and Brain Cancer Discovery Collaborative, Centre for Cancer Research, Hudson Institute of Medical Research, Wright Street, Clayton, Victoria 3168, Australia.|Monash University, Wellington Parade, Clayton, Victoria 3168, Australia.
authors.forename: Vinochani
authors.initials: V
authors.lastname: Pillay
authors.affiliation: Oncogenic Signalling Laboratory and Brain Cancer Discovery Collaborative, Centre for Cancer Research, Hudson Institute of Medical Research, Wright Street, Clayton, Victoria 3168, Australia.|Monash University, Wellington Parade, Clayton, Victoria 3168, Australia.
authors.forename: Terrance G
authors.initials: TG
authors.lastname: Johns
authors.affiliation: School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.|B CUBE Centre for Molecular Bioengineering, TU Dresden, Dresden 01307, Germany.|Department of Chemistry and Food Chemistry, TU Dresden, Dresden 01307, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Kröger
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Future Industries Institute, University of South Australia, Mawson Lakes Boulevard, Mawson Lakes, South Australia 5095, Australia.
authors.forename: Nicolas H
authors.identifier: http://orcid.org/0000-0002-1536-7804
authors.initials: NH
authors.lastname: Voelcker
mesh_terms: D000818:Animals; D000906:Antibodies; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D017377:Diatoms / Q000235:genetics / Q000378:metabolism*; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation; D005818:Genetic Engineering; D007074:Immunoglobulin G; D008081:Liposomes; D016393:Lymphoma, B-Cell / Q000188:drug therapy; D051379:Mice; D008823:Micelles; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009447:Neuroblastoma / Q000188:drug therapy; D010316:Particle Size; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012822:Silicon Dioxide / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D008081:Liposomes; D008823:Micelles; D011993:Recombinant Fusion Proteins; D012822:Silicon Dioxide; D002166:Camptothecin