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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.
PMID
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Authors

Mayor MeshTerms
Keywords

Prostate-specific membrane antigen

multi-walled carbon nanotubes

photothermal cell ablation

prostate cancer

therapeutics

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28351335
OWN - NLM
STAT- MEDLINE
DA  - 20170329
DCOM- 20170407
LR  - 20170407
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 3
DP  - 2017 Mar
TI  - Prostate-specific membrane antigen-directed nanoparticle targeting for extreme
      nearfield ablation of prostate cancer cells.
PG  - 1010428317695943
LID - 10.1177/1010428317695943 [doi]
AB  - 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 &gt;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 (&lt;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.
FAU - Lee, Seung S
AU  - Lee SS
AD  - 1 Segal Cancer Centre and Lady Davis Institute for Medical Research, Jewish
      General Hospital, Montreal, QC, Canada.
AD  - 2 Division of Experimental Medicine, Department of Medicine/Oncology, McGill
      University, Montreal, QC, Canada.
FAU - Roche, Philip Jr
AU  - Roche PJ
AD  - 1 Segal Cancer Centre and Lady Davis Institute for Medical Research, Jewish
      General Hospital, Montreal, QC, Canada.
FAU - Giannopoulos, Paresa N
AU  - Giannopoulos PN
AD  - 1 Segal Cancer Centre and Lady Davis Institute for Medical Research, Jewish
      General Hospital, Montreal, QC, Canada.
FAU - Mitmaker, Elliot J
AU  - Mitmaker EJ
AD  - 1 Segal Cancer Centre and Lady Davis Institute for Medical Research, Jewish
      General Hospital, Montreal, QC, Canada.
AD  - 3 Department of Surgery, McGill University, Montreal, QC, Canada.
FAU - Tamilia, Michael
AU  - Tamilia M
AD  - 4 Division of Endocrinology, Jewish General Hospital, Montreal, QC, Canada.
FAU - Paliouras, Miltiadis
AU  - Paliouras M
AD  - 1 Segal Cancer Centre and Lady Davis Institute for Medical Research, Jewish
      General Hospital, Montreal, QC, Canada.
AD  - 2 Division of Experimental Medicine, Department of Medicine/Oncology, McGill
      University, Montreal, QC, Canada.
FAU - Trifiro, Mark A
AU  - Trifiro MA
AD  - 1 Segal Cancer Centre and Lady Davis Institute for Medical Research, Jewish
      General Hospital, Montreal, QC, Canada.
AD  - 2 Division of Experimental Medicine, Department of Medicine/Oncology, McGill
      University, Montreal, QC, Canada.
AD  - 4 Division of Endocrinology, Jewish General Hospital, Montreal, QC, Canada.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (Antibodies)
RN  - 0 (Antigens, Surface)
RN  - 0 (Nanotubes, Carbon)
RN  - EC 3.4.17.21 (Glutamate Carboxypeptidase II)
RN  - EC 3.4.17.21 (glutamate carboxypeptidase II, human)
SB  - IM
MH  - Antibodies/*administration &amp; dosage/chemistry
MH  - Antigens, Surface/*administration &amp; dosage/chemistry/immunology
MH  - Cell Line, Tumor
MH  - Drug Delivery Systems
MH  - Glutamate Carboxypeptidase II/*administration &amp; dosage/chemistry/immunology
MH  - Humans
MH  - Male
MH  - Nanotubes, Carbon/*chemistry
MH  - Prostatic Neoplasms/*drug therapy/immunology/pathology
OTO - NOTNLM
OT  - Prostate-specific membrane antigen
OT  - multi-walled carbon nanotubes
OT  - photothermal cell ablation
OT  - prostate cancer
OT  - therapeutics
EDAT- 2017/03/30 06:00
MHDA- 2017/04/08 06:00
CRDT- 2017/03/30 06:00
AID - 10.1177/1010428317695943 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Mar;39(3):1010428317695943. doi: 10.1177/1010428317695943.

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