title: Prostate-specific membrane antigen-directed nanoparticle targeting for extreme nearfield ablation of prostate cancer cells.
abstract: Almost all biological therapeutic interventions cannot overcome neoplastic heterogeneity. Physical ablation therapy is immune to tumor heterogeneity, but nearby tissue damage is the limiting factor in delivering lethal doses. Multi-walled carbon nanotubes offer a number of unique properties: chemical stability, photonic properties including efficient light absorption, thermal conductivity, and extensive surface area availability for covalent chemical ligation. When combined together with a targeting moiety such as an antibody or small molecule, one can deliver highly localized temperature increases and cause extensive cellular damage. We have functionalized multi-walled carbon nanotubes by conjugating an antibody against prostate-specific membrane antigen. In our in vitro studies using prostate-specific membrane antigen-positive LNCaP prostate cancer cells, we have effectively demonstrated cell ablation of >80% with a single 30-s exposure to a 2.7-W, 532-nm laser for the first time without bulk heating. We also confirmed the specificity and selectivity of prostate-specific membrane antigen targeting by assessing prostate-specific membrane antigen-null PC3 cell lines under the same conditions (<10% cell ablation). This suggests that we can achieve an extreme nearfield cell ablation effect, thus restricting potential tissue damage when transferred to in vivo clinical applications. Developing this new platform will introduce novel approaches toward current therapeutic modalities and will usher in a new age of effective cancer treatment squarely addressing tumoral heterogeneity.
authors.affiliation: 1 Segal Cancer Centre and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.|2 Division of Experimental Medicine, Department of Medicine/Oncology, McGill University, Montreal, QC, Canada.
authors.forename: Seung S
authors.initials: SS
authors.lastname: Lee
authors.affiliation: 1 Segal Cancer Centre and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.
authors.forename: Philip Jr
authors.initials: PJ
authors.lastname: Roche
authors.affiliation: 1 Segal Cancer Centre and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.
authors.forename: Paresa N
authors.initials: PN
authors.lastname: Giannopoulos
authors.affiliation: 1 Segal Cancer Centre and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.|3 Department of Surgery, McGill University, Montreal, QC, Canada.
authors.forename: Elliot J
authors.initials: EJ
authors.lastname: Mitmaker
authors.affiliation: 4 Division of Endocrinology, Jewish General Hospital, Montreal, QC, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Tamilia
authors.affiliation: 1 Segal Cancer Centre and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.|2 Division of Experimental Medicine, Department of Medicine/Oncology, McGill University, Montreal, QC, Canada.
authors.forename: Miltiadis
authors.initials: M
authors.lastname: Paliouras
authors.affiliation: 1 Segal Cancer Centre and Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.|2 Division of Experimental Medicine, Department of Medicine/Oncology, McGill University, Montreal, QC, Canada.|4 Division of Endocrinology, Jewish General Hospital, Montreal, QC, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Trifiro
mesh_terms: D000906:Antibodies / Q000008:administration & dosage* / Q000737:chemistry; D000954:Antigens, Surface / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D043425:Glutamate Carboxypeptidase II / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008297:Male; D037742:Nanotubes, Carbon / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D000906:Antibodies; D000954:Antigens, Surface; D037742:Nanotubes, Carbon; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: Prostate-specific membrane antigen; multi-walled carbon nanotubes; photothermal cell ablation; prostate cancer; therapeutics