Photodynamic therapy enables tumor-specific ablation in preclinical models of thyroid cancer
Open accessAbstract
The incidence of differentiated thyroid cancer has increased significantly during the last several decades. Surgical resection is the primary treatment for thyroid cancer and is highly effective, resulting in 5-year survival rates greater than 98%. However, surgical resection can result in short- and long-term treatment-related morbidities. Additionally, as this malignancy often affects women less than 40 years of age, there is interest in more conservative treatment approaches and, an unmet need for therapeutic options that minimize the risk of surgery-related morbidities while simultaneously providing an effective cancer treatment. Photodynamic therapy (PDT) has the potential to reduce treatment-related side effects by decreasing invasiveness and limiting toxicity. Owing to multiple advantageous properties of the porphyrin-HDL nanoparticle (PLP) as a PDT agent, including preferential accumulation in tumor, biodegradability and unprecedented photosensitizer packing, we evaluate PLP-mediated PDT as a minimally invasive, tumor-specific treatment for thyroid cancer. On both a biologically relevant human papillary thyroid cancer (K1) mouse model and an anatomically relevant rabbit squamous carcinoma (VX2)-implanted rabbit thyroid model, the intrinsic fluorescence of PLP enabled tracking of tumor preferential accumulation and guided PDT. This resulted in significant and specific apoptosis in tumor tissue, but not surrounding normal tissues including trachea and recurrent laryngeal nerve (RLN). A long-term survival study further demonstrated that PLP-PDT enabled complete ablation of tumor tissue while sparing both the normal thyroid tissue and RLN from damage, thus providing a safe, minimally invasive, and effective alternative to thyroidectomy for thyroid cancer therapies.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Studies on rabbits confirmed significantly higher accumulation of PLP in pathological tissue compared to surrounding muscles or nervous tissue.
“Studies conducted on rabbits confirmed a significantly higher accumulation of PLP in pathological tissue, compared to surrounding muscles or nervous tissue.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [14]
The rabbit thyroid tumor imaging section reports visibly higher PLP accumulation in tumor than in surrounding muscle, and microscopy shows PLP in tumor but not in nearby nerve tissue (Fig. 4). It does not report a statistical significance test for those rabbit comparisons; the significant uptake comparisons in the supplied passages concern mice. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPLP-PDT is safe in relation to nervous tissue.
“which indicates the safety of PDT in relation to the nervous tissue.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [14]
In the rabbit thyroid-tumor model, the PLP-PDT results report normal recurrent laryngeal nerve morphology, minimal apoptosis, and unchanged vocal-cord movement (PLP-enabled effective PDT section; Discussion). These findings support safety for the nerve examined, but not a general claim of safety for nervous tissue. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe most commonly used photosensitizers in PDT for thyroid cancers include hypericin, porphyrin, photophrin, radachlorin, and 5-aminolevulinic acid (ALA).
“The most commonly used PS in PDT for the treatment of thyroid cancers include hypericin, porphyrin, photophrin, radachlorin, and 5-aminolevulinic acid (ALA). [8-10,14,32]”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [14]
The Introduction (page unavailable) describes a porphyrin nanoparticle used for PDT, and the cell-line results report its activity in thyroid cancer cells. Our copy does not identify hypericin, photophrin, radachlorin, or ALA as thyroid-cancer photosensitizers, nor does it establish that the listed agents are the most commonly used. (LLM, conf=0.85)
Experimental — accuracy not yet measuredStudies on the effect of PDT with hypericin, porphyrin, photophrin, radachlorin or 5-aminolevulinic acid as photosensitizer on thyroid cancer have shown promising effects.
“Studies on the effect of PDT with hypericin, porphyrin, photophrin, radachlorin or 5-aminolevulinic acid as PS on thyroid cancer have shown promising effects”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [14]
The Abstract and Discussion report promising results for porphyrin-nanoparticle PDT in preclinical thyroid-cancer models. Our copy does not report thyroid-cancer results for hypericin, photophrin, radachlorin, or 5-aminolevulinic acid, so it supports only the porphyrin part of the list. Page numbers were not supplied. (LLM, conf=0.90)
Experimental — accuracy not yet measuredCytotoxic specificity distinguishes PDT from other methods like ablation; it combines PS predilection for tumor, focusing low-power laser only on tumor, and local action generating ROS rather than dehydration or temperature change.
“Cytotoxic specificity, which distinguishes PDT from other methods, e.g. ablation, is a combination of PS molecules predilection for the tumor, focusing the low-power laser only on the tumor and local action, while generating ROS, not dehydration or temperature change. [14]”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [14]
Both PDT-treated and non-PDT-treated rabbit recurrent laryngeal nerves showed minimal apoptosis and normal morphology.
“Both preparations showed minimal apoptosis and normal morphology”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [14]
Control rabbits with thyroid tumors left untreated or exposed only to laser showed significant tumor progression.
“In comparison to the control groups of rabbits with thyroid tumors left untreated and exposed only to laser, in which significant tumor progression occurred”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [14]
The PLP-PDT study group had a normal image of the neck region in the computed tomography scan.
“as well as a normal image of the neck region in the computed tomography scan.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [14]
The PLP-PDT study group had absence of tumor cells in histological examination of the thyroid after the 53rd day of the study.
“the study group was characterized by the absence of tumor cells in the histological examination of the thyroid after the 53rd day of the study”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [14]
TUNEL staining showed a significant level of apoptosis of tumor cells after PLP-PDT compared to the control group (75.7% vs. 10.6%).
“Additionally, the TUNEL staining test revealed a significant level of apoptosis of tumor cells after PLP-PDT compared to the control group (75.7% vs. 10.6%).”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [14]
Absence of soft tissue pathology was confirmed by comparing the functional state of the recurrent laryngeal nerve before the study, 24 hours after, and 7 days after treatment.
“The absence of soft tissue pathology was also confirmed by comparing the functional state of the recurrent laryngeal nerve with the state before the study, 24 hours after and 7 days after the treatment.”
From Photodynamic Therapy for Thyroid Cancer (2025) · cites this paper as [14]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Schweppe, R. E., Klopper, J. P., Korch, C., Pugazhenthi, U., Benezra, M., Knauf, J. A., Fagin, J. A., Marlow, L. A., Copland, J. A., Smallridge, R. C., et al. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1102 · Cited by 563 · see citing works
Flagged first, then by citations
Research works printed but not linked: 25
- Arora A, Swords C, Garas G, Chaidas K, Prichard A, Budge J, Davies DC & Tolley N 2016 The perception of scar cosmesis following thyroid and parathyroid surgery: a prospective cohort study. International Journal of Surgery 25 38-43. (https://doi.org/10.1016/j. ijsu.2015.11.021) · DOI
- Betz CS, Jager HR, Brookes JA, Richards R, Leunig A & Hopper C 2007 Interstitial photodynamic therapy for a symptom-targeted treatment of complex vascular malformations in the head and neck region. Lasers in Surgery and Medicine 39 571-582. (https://doi.org/10.1002/ lsm.20535) · DOI
- Choi Y, Lee JH, Kim YH, Lee YS, Chang HS, Park CS & Roh MR 2014 Impact of postthyroidectomy scar on the quality of life of thyroid cancer patients. Annals of Dermatology 26 693-699. (https://doi. org/10.5021/ad.2014.26.6.693) · DOI
- Cui L, Lin Q, Jin CS, Jiang W, Huang H, Ding L, Muhanna N, Irish JC, Wang F, Chen J, et al. 2015 A pegylation-free biomimetic porphyrin nanoplatform for personalized cancer theranostics. ACS Nano 9 4484-4495. (https://doi.org/10.1021/acsnano.5b01077) · DOI
- Davies L & Welch HG 2014 Current thyroid cancer trends in the United States. JAMA Otolaryngology: Head and Neck Surgery 140 317-322. (https://doi.org/10.1001/jamaoto.2014. · DOI
- Gambelunghe G, Fede R, Bini V, Monacelli M, Avenia N, D'ajello M, Colella R, Nasini G & De Feo P 2013 Ultrasound-guided interstitial laser ablation for thyroid nodules is effective only at high total amounts of energy: results from a three-year pilot study. Surgical Innovation 20 345-350. (https://doi.org/10.1177/1553350612459276) · DOI
- Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, et al. 2016 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines Task Force on thyroid nodules and differentiated thyroid cancer. Thyroid 26 1-133. (https://doi.org/10.1089/thy.2015.0020) · DOI · Paper page
- Huang X, Jain PK, El-Sayed IH & El-Sayed MA 2006 Determination of the minimum temperature required for selective photothermal destruction of cancer cells with the use of immunotargeted gold nanoparticles. Photochemistry and Photobiology 82 412-417. (https:// doi.org/10.1562/2005-12-14-RA-754) · DOI
- Ito Y, Kudo T, Kobayashi K, Miya A, Ichihara K & Miyauchi A 2012 Prognostic factors for recurrence of papillary thyroid carcinoma in the lymph nodes, lung, and bone: analysis of 5,768 patients with average 10-year follow-up. World Journal of Surgery 36 1274-1278. (https://doi.org/10.1007/s00268-012-1423-5) · DOI
- Jaque D, Martinez Maestro L, Del Rosal B, Haro-Gonzalez P, Benayas A, Plaza JL, Martin Rodriguez E & Garcia Sole J 2014 Nanoparticles for photothermal therapies. Nanoscale 6 9494-9530. (https://doi. org/10.1039/c4nr00708e) · DOI
- La Vecchia C, Malvezzi M, Bosetti C, Garavello W, Bertuccio P, Levi F & Negri E 2015 Thyroid cancer mortality and incidence: a global overview. International Journal of Cancer 136 2187-2195. (https://doi. org/10.1002/ijc.29251) · DOI
- Landerholm K, Wasner AM & Jarhult J 2014 Incidence and risk factors for injuries to the recurrent laryngeal nerve during neck surgery in the moderate-volume setting. Langenbeck's Archives of Surgery 399 509-515. (https://doi.org/10.1007/s00423-013-1154-6) · DOI
- Lim H, Devesa SS, Sosa JA, Check D & Kitahara CM 2017 Trends in thyroid cancer incidence and mortality in the United States, 1974- 2013. JAMA 317 1338-1348. (https://doi.org/10.1001/ jama.2017.2719) · DOI · Paper page
- Lin LM, Chen YK, Chen CH, Chen YW, Huang AH & Wang WC 2009 VX2-induced rabbit buccal carcinoma: a potential cancer model for human buccal mucosa squamous cell carcinoma. Oral Oncology 45 e196-e203. (https://doi.org/10.1016/j.oraloncology.2009.07.012) · DOI
- Moan J & Berg K 1991 The photodegradation of porphyrins in cells can be used to estimate the lifetime of singlet oxygen. Photochemistry and Photobiology 53 549-553. (https://doi.org/10.1111/j.1751-1097.1991. tb03669.x) · DOI
- Muhanna N, Cui L, Chan H, Burgess L, Jin CS, Macdonald TD, Huynh E, Wang F, Chen J, Irish JC, et al. 2015a Multimodal image-guided surgical and photodynamic interventions in head-and-neck cancer: from primary tumor to metastatic drainage. Clinical Cancer Research 22 961-970. (https://doi.org/10.1158/1078-0432.CCR-15-1235) · DOI
- Muhanna N, Jin CS, Huynh E, Chan H, Qiu Y, Jiang W, Cui L, Burgess L, Akens MK, Chen J, et al. 2015b Phototheranostic porphyrin nanoparticles enable visualization and targeted treatment of head and neck cancer in clinically relevant models. Theranostics 5 1428-1443. (https://doi.org/10.7150/thno.13451) · DOI
- Nixon IJ, Angelos P, Shaha AR, Rinaldo A, Williams MD & Ferlito A 2018 Image-guided chemical and thermal ablations for thyroid disease: review of efficacy and complications. Head and Neck 40 2103-2115. (https://doi.org/10.1002/hed.25181) · DOI
- Pacella CM, Mauri G, Achille G, Barbaro D, Bizzarri G, De Feo P, Di Stasio E, Esposito R, Gambelunghe G, Misischi I, et al. 2015 Outcomes and risk factors for complications of laser ablation for thyroid nodules: a multicenter study on 1531 patients. Journal of Clinical Endocrinology and Metabolism 100 3903-3910. (https://doi. org/10.1210/jc.2015-1964) · DOI
- Papaleontiou M, Hughes DT, Guo C, Banerjee M & Haymart MR 2017 Population-based assessment of complications following surgery for thyroid cancer. Journal of Clinical Endocrinology and Metabolism 102 2543-2551. (https://doi.org/10.1210/jc.2017-00255) · DOI
- Parvinian A, Casadaban LC & Gaba RC 2014 Development, growth, propagation, and angiographic utilization of the rabbit VX2 model of liver cancer: a pictorial primer and 'how to' guide. Diagnostic and Interventional Radiology 20 335-340. (https://doi.org/10.5152/ dir.2014.13415) · DOI
- Redrobe S 2002 Calcium metabolism in rabbits. Seminars in Avian and Exotic Pet Medicine 11 94-101. (https://doi.org/10.1053/ saep.2002.125100) · DOI
- Rous P, Kidd JG & Smith WE 1952 Experiments on the cause of the rabbit carcinomas derived from virus-induced papillomas. II. Loss by the Vx2 carcinoma of the power to immunize hosts against the papilloma virus. Journal of Experimental Medicine 96 159-174. (https://doi.org/10.1084/jem.96.2.159) · DOI
- Russell JO, Razavi CR, Garstka ME, Chen LW, Vasiliou E, Kang SW, Tufano RP & Kandil E 2019 Remote-access thyroidectomy: a multi- institutional North American experience with transaxillary, robotic facelift, and transoral endoscopic vestibular approaches. Journal of the American College of Surgeons 228 516-522. (https://doi. org/10.1016/j.jamcollsurg.2018.12.005) · DOI
- Smith J, Douglas J, Smith B, Dougherty T & Ayshford C 2014 Assessment of recurrent laryngeal nerve function during thyroid surgery. Annals of the Royal College of Surgeons of England 96 130-135. (https://doi.org/10.1308/003588414X13814021676594) · DOI
Cited by
Sorted by citations
Photodynamic Therapy for Thyroid Cancer
Inglot, J., Strzelczyk, J. K., Bartusik-Aebisher, D., & Aebisher, D. (2025) · BioMed · doi:10.3390/biomed5010008 · Cited by 2 · see citing works
- Authors
- Muhanna, N., Chan, H. H. L., Townson, J. L., Jin, C. S., Ding, L., Valic, M. S., Douglas, C. M., MacLaughlin, C. M., Chen, J., Zheng, G., & Irish, J. C.
- Affiliations
- University Health Network (CA)
- ORCID
- Venue
- Endocrine-Related Cancer
- Publisher
- Bioscientifica
- Published
- 2020-02
- Volume
- 27
- Issue
- 2
- Pages
- 41-53
- ISSN
- 1351-0088 (ISSN-L)
- 1479-6821
- OpenAlex
- W2991511894
- Cited by
- 26
- References
- 1
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 1
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine Related Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Princess Margaret Cancer Foundation
- Terry Fox Research Institute (PPG#1075, #1075)
- Canadian Cancer Society Research Institute (704718)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- photodynamic therapy, thyroid cancer, papillary thyroid carcinoma, photosensitizers, apoptosis, minimally invasive cancer treatment
- MeSH terms
- Animals, Disease Models, Animal, Humans, Photochemotherapy, Porphyrins, Rabbits, Thyroid Neoplasms, Cell Line, Tumor, Mice, Nanoparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
