Encapsulation of IR783 in UiO-66 MOFs for Improved Photodynamic Efficacy Against Breast Cancer Cells
- Department of Chemistry, Science Faculty, İzmir Institute of Technology, 35430, İzmir, Türkiye
Copyright (c) 2025 Sinem Şahinoğlu , Gülşah Şanlı-Mohamed (Author)

This work is licensed under a Creative Commons Attribution 4.0 International License.
How to Cite
Abstract
Breast cancer remains the most prevalent malignancy among women worldwide, underscoring the need for innovative therapeutic strategies beyond conventional modalities. Photodynamic therapy (PDT) offers a non-invasive approach that leverages light-activated photosensitizers to induce reactive oxygen species (ROS)-mediated tumor cell death. IR783, a near-infrared fluorescent (NIRF) heptamethine cyanine dye, has shown promise as a theranostic agent in cancer therapy due to its tumor-selective uptake and pro-apoptotic effects. However, its clinical potential is hindered by poor stability, rapid dissociation in polar environments, low quantum yield, and suboptimal tumor accumulation. In this study, we developed a multifunctional nanoplatform by encapsulating IR783 into UiO-66, a zirconium-based metal-organic framework (MOF), to enhance the delivery and photodynamic performance of the dye (IR783@UiO-66). The system was structurally characterized, and its biocompatibility and drug release profiles were evaluated. In vitro experiments were conducted to assess the cytotoxic and phototoxic effects of IR783, UiO-66, and IR783@UiO-66 on breast cancer cell lines (MCF-7, MDA-MB-231) and normal breast epithelial cells (MCF-10A), under LED irradiation at varying light intensities (18–144 J/cm²) and exposure durations (7.5–60 min). The results demonstrated that IR783@UiO-66 significantly reduced cancer cell viability in a dose- and light-dependent manner while sparing normal cells. Free IR783 showed slightly higher phototoxicity, attributed to differences in release kinetics and loading efficiency. UiO-66 alone exhibited negligible cytotoxicity under irradiation, confirming its safety profile. This study highlights the potential of UiO-66 as a promising nanocarrier for enhancing IR783-mediated PDT, offering a synergistic strategy for targeted and efficient breast cancer therapy.
Keywords
- Photodynamic therapy (PDT),
- Breast cancer,
- IR783,
- UiO-66,
- Metal-organic frameworks (MOFs)
References
- Aggarwal P, Hall JB, McLeland CB, Dobrovolskaia MA, McNeil SE (2009) Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility, and therapeutic efficacy. Adv Drug Deliv Rev 61(6):428–437. https://doi.org/10.1016/j.addr.2009.03.009
- Ahmad A (2019) Breast cancer statistics: recent trends. Adv Exp Med Biol 1152:1–7. https://doi.org/10.1007/978-3-030-20301-6_1
- Ahmadi M, Ayyoubzadeh S, Ghorbani-Bidkorpeh F, et al (2021) An investigation of affecting factors on MOF characteristics for biomedical applications: A systematic review. Heliyon 7:e06914. https://doi.org/10.1016/j.heliyon.2021.e06914
- Bazzazan S, Gholipour M, Mahjoub AR (2023) Thermal decomposition mechanism of UiO-66 MOFs: Role of solvent and organic linker. Microporous Mesoporous Mater 354:112993. https://doi.org/10.1016/j.micromeso.2022.112993
- Bellido E, Guillevic M, Hidalgo T, Santander-Ortega MJ, Serre C, Horcajada P (2015) Understanding the colloidal stability of the mesoporous MIL-100 (Fe) nanoparticles in physiological media. Langmuir 31(44):12301–12309. https://doi.org/10.1021/acs.langmuir.5b02967
- Bonnett R (2000) Chemical Aspects of Photodynamic Therapy. Gordon and Breach Science Publishers, London
- Bown SG (2013) Photodynamic therapy for photochemists. Photochem Photobiol Sci 12(7):1187–1190.
- Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72(1–2):248–254. https://doi.org/10.1016/0003-2697(76)90527-3
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492
- Brown SB, Brown EA, Walker I (2004) The present and future role of photodynamic therapy in cancer treatment. Lancet Oncol 5(8):497–508. https://doi.org/10.1016/S1470-2045(04)01529-3
- Busch TM (2010) Localized treatment using photodynamic therapy for tumors: current clinical applications and future directions. J Natl Compr Canc Netw 8(4):427–434. https://doi.org/10.6004/jnccn.2010.0023
- Castano AP, Mroz P, Hamblin MR (2006) Photodynamic therapy and anti-tumour immunity. Nat Rev Cancer 6(7):535–545. https://doi.org/10.1038/nrc1894
- Cengel KA, Simone CB, Glatstein E (2016) PDT: mechanisms and clinical use. J Clin Oncol 34(19):2173–2180.
- Chen H, Zhao J, Zhu W-H. Recent progress in the development of organic photodynamic therapy photosensitizers. Chem Soc Rev. 2021;50(5):2873–2940. https://doi.org/10.1039/D0CS01056D
- Cheng H, Wang K, Tian J, Ren W, Zou R, Yang Z, et al (2016) Multifunctional nanoparticles for photodynamic therapy and imaging of breast cancer. Nanoscale 8(3):1503–1510. https://doi.org/10.1039/C5NR07431D
- Cole M, Hall D, Wiles R, et al (2011) Serum protein binding of drugs during and after pregnancy in humans. Clin Pharmacol Ther 90(5):766–773. https://doi.org/10.1038/clpt.2011.178
- Czarnecka-Czapczyńska M, Czarnecki P, Krajewska B (2021) Photodynamic therapy in cancer treatment: Challenges and opportunities. Molecules 26(4):1192. https://doi.org/10.3390/molecules26041192
- Decker GE, Stillman Z, Attia L, et al (2019) Controlling size, defectiveness, and fluorescence in nanoparticle UiO-66 through water and ligand modulation. Chem Mater 31(13):4831–4839. https://doi.org/10.1021/acs.chemmater.9b01091
- Deng J, Wang L, Wang B, Yu X, Mao W (2017) Targeted drug delivery system for breast cancer therapy: Enhanced by the EPR effect. Drug Dev Res 78(6):283–293. https://doi.org/10.1002/ddr.21397
- Dobrovolskaia MA, Germolec DR, Weaver JL (2009) Evaluation of nanoparticle immunotoxicity. Nat Nanotechnol 4(7):411–414. https://doi.org/ 10.1038/nnano.2009.175
- Eruslanov E, Kusmartsev S (2010) Identification of ROS using oxidized DCFDA and flow-cytometry. Methods Mol Biol 594:57–72. https://doi.org/10.1007/978-1-60761-411-1_4
- Fan W, Huang P, Chen X (2016) Overcoming the Achilles’ heel of photodynamic therapy. Chem Soc Rev 45(23):6488–6519. https://doi.org/10.1039/C6CS00375H
- Feng Y, Liu Y, Li C, Yu L, Huang J (2022) In vitro release mechanism and cytotoxic behavior of protein-based nanoparticles. Braz J Pharm Sci 58:e19098. https://doi.org/10.1590/s2175-97902019000219098
- Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al (2021) Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. https://gco.iarc.fr/today
- Fisher B, Anderson S, Redmond CK, Wolmark N, Wickerham DL, Cronin WM (1995) Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation. N Engl J Med 333(22):1456–1461. https://doi.org/10.1056/NEJM199511303332203
- Frangioni JV (2003) In vivo near-infrared fluorescence imaging. Curr Opin Chem Biol 7(5):626–634. https://doi.org/10.1016/j.cbpa.2003.08.007
- Gao H, Zhang Y, Guo X, Sun J (2018) Synthesis and characterization of nanoscale UiO-66 with high crystallinity for drug delivery applications. Microporous Mesoporous Mater 271:45–51. https://doi.org/10.1016/j.micromeso.2018.05.021
- Gao W, Zhang Y, Zhang L, Pang X, Wang S, Guo Z, et al (2018) Post-synthetic modification of UiO-66 for biomedical applications. ACS Appl Mater Interfaces 10(1):345–352. https://doi.org/10.1021/acsami.7b15434
- Horcajada P, Chalati T, Serre C, et al (2012) Metal–organic frameworks as efficient materials for drug delivery. Angew Chem Int Ed Engl 51(4):1047–1051. https://doi.org/10.1002/anie.200601878
- Houghton J, George WD, Cuzick J, Duggan C, Fentiman IS, Spittle M (2003) Radiotherapy and tamoxifen after breast-conserving surgery. N Engl J Med 347(16):1233–1241. https://doi.org/10.1016/S0140-6736(03)13859-7
- Hu Z, Zhao D (2015) Degradable MOFs for drug delivery. Adv Mater 27(39):5309–5324. https://doi.org/10.1002/adma.201501084
- Kandiah M, Nilsen MH, Usseglio S, et al (2010) Synthesis and stability of tagged UiO-66 metal–organic frameworks. Chem Mater 22(24):6632–6640. https://doi.org/10.1021/cm1022882
- Leon-Ferre RA, Lau YK, Smith ML, Thompson RA, Hieken TJ, Boughey JC, et al (2018) Male breast cancer: A disease distinct from female breast cancer. Breast Cancer Res Treat 173(1):37–48.
- Li B, Wen H, Cui Y, Zhou W, Qian G, Chen B (2016) Metal-organic frameworks for oxygen storage and release. J Mater Chem B 4(34):6244–6260. https://doi.org/10.1039/C6TB01100D
- Li C, Zhang Y, Wang W, Liu Z, Wang L, Gao W, et al (2019) Advances in nanomedicine for breast cancer treatment. Biomaterials 221:119416.
- Li L, Hou J, Liu X, Wang Z (2021) Acid-responsive nanocarriers for drug delivery in cancer therapy. J Nanobiotechnol 19(1):355. https://doi.org/10.1186/s12951-021-01048-4
- Liang W, Ricco R, Doherty CM, et al (2019) Metal–organic framework-based nanomedicine platforms for drug delivery. Adv Mater 31(19):1900331. https://doi.org/10.1002/adma.201900331
- Lismont M, Dreesen L, Wuttke S (2017) Metal-organic framework nanoparticles in photodynamic therapy: Current status and perspectives. Adv Funct Mater 27(14):1606314. https://doi.org/10.1002/adfm.201606314
- Lucky SS, Soo KC, Zhang Y (2015) Nanoparticles in photodynamic therapy. Chem Rev 115(4):1990–2042. https://doi.org/10.1021/cr5004198
- Luo S, Zhang E, Su Y, Cheng T, Shi C (2013) A review of NIR dyes in cancer targeting and imaging. Biomaterials 34(28):6952–6964. https://doi.org/10.1016/j.biomaterials.2013.05.009
- Mayer A, Vadon M, Rinner B, et al (2009) The role of nanoparticle size and surface charge in hemolytic activity of silica nanoparticles. Nanotoxicology 3(1):33–42. https://doi.org/10.1080/17435390902788004
- Mi Y, Wang Y, Liang X, et al (2021) Cytotoxicity assessment of gold nanoparticles and laser-induced photothermal therapy in cancer treatment. J Biomed Nanotechnol 17(6):1095–1106. https://doi.org/10.1166/jbn.2021.3111
- Motegi T, Uemura T, Kitagawa S (2017) A facile synthesis of UiO-66 systems and their hydrothermal stability. J Hazard Mater 321:390–400. https://doi.org/10.1016/j.jhazmat.2016.09.065
- Mottram LF, Boens N, Sliwa M, et al (2006) Hydrophobic analogues of rhodamine B and rhodamine 101: Potent fluorescent probes. J Med Chem 49(24):7323–7332. https://doi.org/10.1021/jm060596a
- Nasrabadi M, Ghasemzadeh MA, Zand Monfared MR (2019) A new Zr-based metal–organic framework: Synthesis, characterization, and application in dye adsorption. Microporous Mesoporous Mater 278:91–99. https://doi.org/10.1016/j.micromeso.2018.11.008
- Parkes MV, Greathouse JA, Hart D, Gallis DF, Nenoff TM (2016) Modeling of gas adsorption in MOFs for medical applications. Microporous Mesoporous Mater 225:494–503.
- Piscopo I, Galietta A, Tosco A, Curcio A, Berlier G, Arpicco S, et al (2016) Biomedical applications of zirconium-based MOFs. Int J Pharm 512(1):132–140. https://doi.org/10.1016/j.ijpharm.2016.08.024
- Prabhu S, Selvakumar S, Saravanakumar K (2021) Enhanced solubility and stability of hydrophobic drugs using MOF-based nanocarriers: XRD and structural analysis. J Mater Chem B 9(17):3781–3790. https://doi.org/10.1039/D0TB02914F
- Radzi R, Rahman WAWA, Zaini MA, Hashim U, Omar R, et al (2011) Near-infrared dyes for cancer imaging. Sens Actuators B Chem 160(1):845–870. https://doi.org/10.1016/j.snb.2011.08.004
- Rami M, Al-Enizi AM, Elzatahry AA (2021) Thermal behavior and decomposition mechanism of dye-loaded metal–organic frameworks. J Therm Anal Calorim 146(6):2659–2668. https://doi.org/10.1007/s10973-020-10250-6
- Sampath M, Pichaimani A, Kumpati P, Sengottuvelan B (2020) Breast cancer statistics and emerging trends. Curr Probl Cancer 44(6):100504.
- Schoedel A, Li M, Li D, O’Keeffe M, Yaghi OM (2016) Structures of metal–organic frameworks with rod secondary building units. Chem Rev 116(19):12466–12535. https://doi.org/10.1021/acs.chemrev.6b00346
- Semete B, Booysen L, Kalombo L, et al (2012) Effects of protein binding on the biodistribution of PEGylated PLGA nanoparticles. Int J Pharm 424(1–2):400–406. https://doi.org/10.1016/j.ijpharm.2012.02.025
- Shao J, Zheng X, Liu W, Yu Q, Zhang Y, Wang C, et al (2014) IR-783 dye-based cancer cell targeting and imaging. Biomater Sci 2(7):952–960. https://doi.org/10.1039/C4BM00036C
- Song X, Wang X, Xie Z (2021) Addressing tumor hypoxia in PDT using MOFs. J Control Release 337:513–529. https://doi.org/10.1016/j.jconrel.2021.08.034
- Sun J, Xie X, Zhu J, Wang X, Chen S, Zhang L, et al (2017) Combination therapy using PDT and immune checkpoint blockade. ACS Nano 11(6):6090–6101. https://doi.org/10.1021/acsnano.7b01270
- Tan X, Luo S, Wang D, Yang X, Shi C (2012) Development of IR-783 based theranostic agents. ACS Appl Mater Interfaces 4(12):3432–3438. https://doi.org/10.1021/am300753s
- Tang Q, Liu Y, Zhang J, Chen Y, Wang Y, Zhao H, et al (2018) IR-783 induces mitochondrial fission in breast cancer. Mol Pharm 15(5):1929–1934. https://doi.org/10.1021/acs.molpharmaceut.7b01165
- Tang Y, Wang Y, Liu Y, Zhang L, Wu H, Zhao M, et al (2016) PDT efficacy and oxygen limitation. J Photochem Photobiol B 155:60–65. https://doi.org/10.1016/j.jphotobiol.2015.12.011
- Trickett CA, Gagnon KJ, Lee S, et al (2017) The chemistry of metal–organic frameworks for CO₂ capture, regeneration, and conversion. Chem Rev 117(2):861–922. https://doi.org/10.1021/acs.chemrev.6b00367
- Usama SM, Thavornpradit S, Burgess K (2018) Impact of photobleaching on the efficacy of near-infrared photosensitizers for photodynamic therapy. Photochem Photobiol 94(6):1197–1204. https://doi.org/10.1111/php.12929
- Usama SM, Thavornpradit S, Burgess K (2018) Optimized heptamethine cyanines for photodynamic therapy. ACS Appl Bio Mater 1(4):1195–1205. https://doi.org/10.1021/acsabm.8b00141
- Veisi H, Abrifam M, Kamangar S, et al (2021) Pd immobilization on biguanidine-modified Zr-UiO-66 MOF as a reusable heterogeneous catalyst in Suzuki–Miyaura coupling. Sci Rep 11:21883. https://doi.org/10.1038/s41598-021-00991-3
- Wang C, Nesterov EE (2019) Amplifying fluorescent conjugated polymer sensor for singlet oxygen detection. Chem Commun 55(62):8955–8958. https://doi.org/10.1039/C9CC04555F
- Wang H, Joseph JA (1999) Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 27(5–6):612–616. https://doi.org/10.1016/S0891-5849(99)00107-0
- Wang S, Chen Y, Wang S, Li P, Shen Y (2020) pH-sensitive MOF-based drug delivery systems for controlled release and cancer therapy. ACS Appl Mater Interfaces 12(18):20257–20269. https://doi.org/10.1021/acsami.0c04881
- Wilkinson F, Helman WP, Ross AB. Rate constants for the decay and reactions of the lowest electronically excited singlet state of molecular oxygen in solution. J Phys Chem Ref Data. 1995;24(2):663–1021. https://doi.org/10.1063/1.555965
- Wu JB, Lin H, Gao Y, Zhang Z, Chen Y, Wang J, et al (2015) IR-783-based cancer imaging and therapy. Theranostics 5(5):482–496. https://doi.org/10.7150/thno.10485
- Wu MX, Yang YW (2017) Metal–organic framework (MOF)-based drug delivery. Adv Mater 29(23):1606134. https://doi.org/10.1002/adma.201606134
- Wu S, Ge Y, Wang Y, et al (2017) Adsorption of Cr(VI) on nano UiO-66-NH₂ MOFs in water. Environ Technol 39(11):1451–1460. https://doi.org/10.1080/09593330.2017.1327945
- Yallapu MM, Chauhan N, Othman SF, et al (2015) Curcumin nanoformulations: A future nanomedicine for cancer. Nanomedicine 10(2):257–270. https://doi.org/10.2217/nnm.14.113
- Yang X, Shi K, Hao Y, et al (2020) Fluorescence lifetime imaging for monitoring the delivery of nanomedicines in tumor microenvironment. ACS Nano 14(6):6720–6731. https://doi.org/10.1021/acsnano.9b10077
- Yang Z, Song J, Liang C, Chen X (2021) Nanomaterial-assisted photodynamic therapy: Enhancement strategies and biomedical applications. Chem Soc Rev 50(14):7943–7980. https://doi.org/10.1039/D0CS01199F
- Yavuz B, Caner G, Günay G, et al (2024) Development and photophysical characterization of theranostic nanomaterials for cancer phototherapy. J Photochem Photobiol B 243:114965. https://doi.org/10.1016/j.jphotobiol.2022.114965
- Zhou Z, Song J, Tian R, Yang Z, Yu G, Lin L, Zhang G, Fan W, Zhang F, Niu G, Nie L, Chen X (2017) Activatable Singlet Oxygen Generation from Lipid Hydroperoxide Nanoparticles for Cancer Therapy. Angew Chem Int Ed Engl. 56(23):6492-6496. https://doi.org/10.1002/anie.201701181
- Zhou X, Liu X, Wang L, Zhang Y (2025) Characterization of heptamethine cyanine dyes and their application in biomedical imaging. J Photochem Photobiol B 215:112321. https://doi.org/10.1016/j.jphotobiol.2020.112321