title: Engineering A11 Minibody-Conjugated, Polypeptide-Based Gold Nanoshells for Prostate Stem Cell Antigen (PSCA)-Targeted Photothermal Therapy.
abstract: Currently, there is no curative treatment for advanced metastatic prostate cancer, and options, such as chemotherapy, are often nonspecific, harming healthy cells and resulting in severe side effects. Attaching targeting ligands to agents used in anticancer therapies has been shown to improve efficacy and reduce nonspecific toxicity. Furthermore, the use of triggered therapies can enable spatial and temporal control over the treatment. Here, we combined an engineered prostate cancer-specific targeting ligand, the A11 minibody, with a novel photothermal therapy agent, polypeptide-based gold nanoshells, which generate heat in response to near-infrared light. We show that the A11 minibody strongly binds to the prostate stem cell antigen that is overexpressed on the surface of metastatic prostate cancer cells. Compared to nonconjugated gold nanoshells, our A11 minibody-conjugated gold nanoshell exhibited significant laser-induced, localized killing of prostate cancer cells in vitro. In addition, we improved upon a comprehensive heat transfer mathematical model that was previously developed by our laboratory. By relaxing some of the assumptions of our earlier model, we were able to generate more accurate predictions for this particular study. Our experimental and theoretical results demonstrate the potential of our novel minibody-conjugated gold nanoshells for metastatic prostate cancer therapy.
authors.affiliation: 1 Department of Bioengineering, University of California, Los Angeles, CA, USA.
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Mayle
authors.affiliation: 1 Department of Bioengineering, University of California, Los Angeles, CA, USA.
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Dern
authors.affiliation: 1 Department of Bioengineering, University of California, Los Angeles, CA, USA.
authors.forename: Vincent K
authors.initials: VK
authors.lastname: Wong
authors.affiliation: 1 Department of Bioengineering, University of California, Los Angeles, CA, USA.
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Chen
authors.affiliation: 2 Department of Electrical Engineering, University of California, Los Angeles, CA, USA.
authors.forename: Shijun
authors.initials: S
authors.lastname: Sung
authors.affiliation: 1 Department of Bioengineering, University of California, Los Angeles, CA, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.affiliation: 1 Department of Bioengineering, University of California, Los Angeles, CA, USA.
authors.forename: April R
authors.initials: AR
authors.lastname: Rodriguez
authors.affiliation: 3 Department of Molecular and Medical Pharmacology, University of California, Los Angeles CA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Knowles
authors.affiliation: 1 Department of Bioengineering, University of California, Los Angeles, CA, USA.|4 Department of Surgery, University of California, Los Angeles, CA, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Taylor
authors.affiliation: 1 Department of Bioengineering, University of California, Los Angeles, CA, USA.|5 Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.|6 California NanoSystems Institute, University of California, Los Angeles, CA, USA.
authors.forename: Z Hong
authors.initials: ZH
authors.lastname: Zhou
authors.affiliation: 1 Department of Bioengineering, University of California, Los Angeles, CA, USA.|2 Department of Electrical Engineering, University of California, Los Angeles, CA, USA.|4 Department of Surgery, University of California, Los Angeles, CA, USA.
authors.forename: Warren S
authors.initials: WS
authors.lastname: Grundfest
authors.affiliation: 3 Department of Molecular and Medical Pharmacology, University of California, Los Angeles CA, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Wu
authors.affiliation: 1 Department of Bioengineering, University of California, Los Angeles, CA, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Deming
authors.affiliation: 1 Department of Bioengineering, University of California, Los Angeles, CA, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Kamei
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018481:Convection; D058851:GPI-Linked Proteins / Q000378:metabolism; D006046:Gold / Q000378:metabolism*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007136:Immunoglobulins / Q000378:metabolism*; D007259:Infrared Rays; D028022:Low-Level Light Therapy; D008297:Male; D008954:Models, Biological; D008962:Models, Theoretical; D058990:Molecular Targeted Therapy / Q000379:methods*; D057145:Nanoshells / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010789:Phototherapy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000628:therapy; D020349:Surface Plasmon Resonance
chemical_list: D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D007136:Immunoglobulins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; D006046:Gold
keywords: gold nanoshells; photothermal therapy; polypeptide vesicles