A histological evaluation and in vivo assessment of intratumoral near infrared photothermal nanotherapy-induced tumor regression.
OBJECTIVE
Nanoparticle (NP)-enabled near infrared (NIR) photothermal therapy has realized limited success in in vivo studies as a potential localized cancer therapy. This is primarily due to a lack of successful methods that can prevent NP uptake by the reticuloendothelial system, especially the liver and kidney, and deliver sufficient quantities of intravenously injected NPs to the tumor site. Histological evaluation of photothermal therapy-induced tumor regression is also neglected in the current literature. This report demonstrates and histologically evaluates the in vivo potential of NIR photothermal therapy by circumventing the challenges of intravenous NP delivery and tumor targeting found in other photothermal therapy studies.


METHODS
Subcutaneous Cal 27 squamous cell carcinoma xenografts received photothermal nanotherapy treatments, radial injections of polyethylene glycol (PEG)-ylated gold nanorods and one NIR 785 nm laser irradiation for 10 minutes at 9.5 W/cm(2). Tumor response was measured for 10-15 days, gross changes in tumor size were evaluated, and the remaining tumors or scar tissues were excised and histologically analyzed.


RESULTS
The single treatment of intratumoral nanorod injections followed by a 10 minute NIR laser treatment also known as photothermal nanotherapy, resulted in ~100% tumor regression in ~90% of treated tumors, which was statistically significant in a comparison to the average of all three control groups over time (P<0.01).


CONCLUSIONS
Photothermal nanotherapy, or intratumoral nanorod injections followed by NIR laser irradiation of tumors and tumor margins, demonstrate the potential of NIR photothermal therapy as a viable localized treatment approach for primary and early stage tumors, and prevents NP uptake by the reticuloendothelial system.
Department of Physics, Center for Optical Sensors and Spectroscopies, The University of Alabama at Birmingham, Birmingham, AL, USA ; Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL, USA.
Hadiyah N
HN
Green
Department of Pediatrics, Division of Neonatology, The University of Alabama at Birmingham, Birmingham, AL, USA.
Stephanie D
SD
Crockett
Department of Physics, Center for Optical Sensors and Spectroscopies, The University of Alabama at Birmingham, Birmingham, AL, USA.
Dmitry V
DV
Martyshkin
Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL, USA ; Department of Medicine, Division of Preventive Medicine, Biostatistics and Bioinformatics Shared Facility, The University of Alabama at Birmingham, Birmingham, AL, USA.
Karan P
KP
Singh
Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL, USA ; Department of Pathology, Division of Otolaryngology, Head and Neck Surgery, The University of Alabama at Birmingham, Birmingham, AL, USA.
William E
WE
Grizzle
Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL, USA ; Department of Surgery, Division of Otolaryngology, Head and Neck Surgery, The University of Alabama at Birmingham, Birmingham, AL, USA.
Eben L
EL
Rosenthal
Department of Physics, Center for Optical Sensors and Spectroscopies, The University of Alabama at Birmingham, Birmingham, AL, USA.
Sergey B
SB
Mirov
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006046:Gold / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007834:Lasers; D051379:Mice; D008819:Mice, Nude; D043942:Nanotubes / Q000737:chemistry*; D010789:Phototherapy / Q000379:methods*; D011092:Polyethylene Glycols; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D006046:Gold
PEGylation; cancer treatment; gold nanorods; intratumoral; laser therapy; malignancy; nanoparticles; photothermal cancer therapy