Prostate-specific membrane antigen–directed nanoparticle targeting for extreme nearfield ablation of prostate cancer cells

• Published in: Tumor biology Vol. 39; no. 3; p. 1010428317695943
• Main Authors: Lee, Seung S, Roche, Philip JR, Giannopoulos, Paresa N, Mitmaker, Elliot J, Tamilia, Michael, Paliouras, Miltiadis, Trifiro, Mark A
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.03.2017; Sage Publications Ltd; IOS Press
• Subjects: Ablation; Antibodies - administration & dosage; Antibodies - chemistry; Antigens; Antigens, Surface - administration & dosage; Antigens, Surface - chemistry; Antigens, Surface - immunology; Cell Line, Tumor; Chemistry; Drug Delivery Systems; Glutamate Carboxypeptidase II - administration & dosage; Glutamate Carboxypeptidase II - chemistry; Glutamate Carboxypeptidase II - immunology; Humans; Lasers; Light; Localization; Male; Nanoparticles; Nanotubes; Nanotubes, Carbon - chemistry; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - immunology; Prostatic Neoplasms - pathology; Therapeutic applications; Values; United States > US; therapeutics; prostate cancer; Prostate-specific membrane antigen; photothermal cell ablation; multi-walled carbon nanotubes
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1177/1010428317695943

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.