Nanomedicine Journal

Nanomedicine Journal

Evaluation of 5-aminolevulinic acid-functionalized gold nanoclusters for combined photodynamic and radiation therapy in K562 leukemia cells

Document Type : Research Paper

Authors
1 Department of Radiology, School of Allied Medical Sciences, Hamadan University of Medical Sciences, Hamadan, Iran
2 Department of Health Information Technology, School of Allied Medical Sciences, Hamadan University of Medical Sciences, Hamadan, Iran
3 Department of Medical Laboratory Sciences, School of Paramedicine, Hamadan University of Medical Sciences, Hamadan, Iran
4 Department of Medical Physics, School of Medicine Hamadan University of Medical Sciences
5 Dental Implant Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
Abstract
Objective(s): The present work investigated the therapeutic potential of 5-aminolevulinic acid-functionalized gold nanoparticles (5-ALA-AuNPs) when combined with radiotherapy (RT) and photodynamic therapy (PDT) in K562 leukemia cells. Particular attention was given to whether altering the order in which RT and PDT were administered could affect the resulting therapeutic response.
Materials and Methods: For the treatment experiments, K562 cells were plated in 96-well culture plates at 10,000 cells per well. The cells were then exposed to 5-ALA-AuNPs at three concentrations (1.25, 0.625, and 0.3125 mg/mL). Treatment groups were subsequently subjected to either laser irradiation (810 nm, 0.1 W for 60 s), X-ray exposure (2 or 4 Gy at 6 MeV), or a combination of the two modalities administered in different sequences. Viability was quantified by the MTT assay 48 h following completion of the treatments.
Results: Among all treatment regimens, the administration of laser irradiation prior to X-ray exposure at 4 Gy in the presence of 5-ALA-AuNPs resulted in the lowest cell survival rate (27.01%). Higher nanoparticle concentrations correlated with greater cytotoxicity. The treatment sequence significantly impacted outcomes, with the "laser-before-radiotherapy" protocol demonstrating superior efficacy.
Conclusions: 5-ALA-AuNPs exhibit potential as dual radiosensitizing and photosensitizing agents. The sequence of irradiation is a critical determinant of therapeutic outcome, with laser priming prior to RT showing the greatest promise. However, due to the absence of detailed physicochemical characterization and mechanistic validation (e.g., ROS, apoptosis, cellular uptake), these findings are preliminary. Further studies are essential to confirm clinical applicability.
Keywords
Subjects

1.     Alsaab HO, Alghamdi MS, Alotaibi AS, Alzhrani R, Alwuthaynani F, Althobaiti YS, et al. Progress in clinical trials of photodynamic therapy for solid tumors and the role of nanomedicine. Cancers (Basel). 2020;12(10):2793.
2.     Meyer P, Noblet V, Mazzara C, Lallement A. Survey on deep learning for radiotherapy. Comput Biol Med. 2018;98:126-146.
3.     Begg AC, Stewart FA, Vens C. Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer. 2011;11(4):239-253.
4.     Vissink A, Jansma J, Spijkervet F, Burlage F, Coppes R. Oral sequelae of head and neck radiotherapy. Crit Rev Oral Biol Med. 2003;14(3):199-212.
5.     Brown SB, Brown EA, Walker I. The present and future role of photodynamic therapy in cancer treatment. Lancet Oncol. 2004;5(8):497-508.
6.     Dolmans DEJGJ, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nat Rev Cancer. 2003;3(5):380-387.
7.     dos Santos AlF, De Almeida DRQ, Terra LF, Baptista McS, Labriola L. Photodynamic therapy in cancer treatment—an update review. J Cancer Metastasis Treat. 2019;5:25.
8.     Mohammadi Z, Sazgarnia A, Rajabi O, Seilanian Toosi M. Comparative study of X-ray treatment and photodynamic therapy by using 5-aminolevulinic acid conjugated gold nanoparticles in a melanoma cell line. Artif Cells Nanomed Biotechnol. 2017;45(3):467-473.
9.     Kim HS, Lee DY. Near-infrared-responsive cancer photothermal and photodynamic therapy using gold nanoparticles. Polymers (Basel). 2018;10(9):961.
10.  Khaing Oo MK, Yang X, Du H, Wang H. 5-aminolevulinic acid-conjugated gold nanoparticles for photodynamic therapy of cancer. 2008. [Unpublished/Conference].
11.  Shinoda Y, Kato D, Ando R, Endo H, Takahashi T, Tsuneoka Y, et al. Systematic review and meta-analysis of in vitro anti-human cancer experiments investigating the use of 5-aminolevulinic acid (5-ALA) for photodynamic therapy. Pharmaceuticals. 2021;14(3):229.
12.  Pignatelli P, Umme S, D'Antonio DL, Piattelli A, Curia MC. Reactive oxygen species produced by 5-aminolevulinic acid photodynamic therapy in the treatment of cancer. Int J Mol Sci. 2023;24(10):8964.
13.  Lopez RFV, Lange N, Guy R, Bentley MVLB. Photodynamic therapy of skin cancer: controlled drug delivery of 5-ALA and its esters. Adv Drug Deliv Rev. 2004;56(1):77-94.
14.  Kuzelová K, Grebenová D, Pluskalová M, Marinov I, Hrkal Z. Early apoptotic features of K562 cell death induced by 5-aminolaevulinic acid-based photodynamic therapy. J Photochem Photobiol B. 2004;73(2):67-78.
15.  Hirose K, Monzen S, Sato H, Sato M, Aoki M, Hatayama Y, et al. Megakaryocytic differentiation in human chronic myelogenous leukemia K562 cells induced by ionizing radiation in combination with phorbol 12-myristate 13-acetate. J Radiat Res. 2013;54(3):438-446.
16.  Xin Y, Zhang HB, Tang TU, Liu GH, Wang JS, Jiang G, et al. Low‑dose radiation‑induced apoptosis in human leukemia K562 cells through mitochondrial pathways. Mol Med Rep. 2014;10:1569-1575.
17.  Xu W, Luo T, Li P, Zhou C, Cui D, Pang B, et al. RGD-conjugated gold nanorods induce radiosensitization in melanoma cancer cells by downregulating αvβ3 expression. Int J Nanomed. 2012;7:915-924.
18.  Mousavi M, Fereshteh Koosha F, Neshastehriz A. Chemo-radiation therapy of U87-MG glioblastoma cells using SPIO@AuNP-Cisplatin-Alginate nanocomplex. Heliyon. 2023;9:e13847.
19.  Adamczuk GM, Humeniuk E, Adamczuk K, Madej-Czerwonka B, Dudka J. Disruption of mitochondrial function augments the radiosensitivity of prostate cancer cell lines. Ann Agric Environ Med. 2023;30(1):65-76.
20.  Maddah A, Ziamajidi N, Khosravi H, Danesh H, Abbasalipourkabir R. Gold nanoparticles induce apoptosis in HCT-116 colon cancer cell line. Mol Biol Rep. 2022;49(8):7863-7871.
21.  Khosravi H, Doosti-Irani A, Bouraghi H, Nikzad S. Investigation of gold nanoparticles effects in radiation therapy of cancer: a systematic review. J Adv Med Biomed Res. 2022;30(142):388-396.
22.  Khosravi H, Ghazikhanlousani K, Rahimi A. Use of gold nanoparticles in MAGIC-f gels to 18 MeV photon enhancement. Nanomed J. 2019;6(1).
23.  Khosravi H, Manoochehri H, Farmany A, Khoshghadam A, Rafieemehr H, Azmoonfar R. Bismuth selenide nanoparticles enhance radiation sensitivity in colon cancer cells in-vitro. Biochem Biophys Rep. 2024;38:101732.

Articles in Press, Accepted Manuscript
Available Online from 03 November 2026