Abstract
Photodynamic therapy (PDT) has recently become significant as a clinical modality for cancer therapy and multidrug-resistant (MDR) infections, replacing conventional chemotherapy and radiation therapy protocols. PDT involves the excitation of certain nontoxic molecules called photosensitizers (PS), applying a specific wavelength of light to generate reactive oxygen species (ROS) to treat cancer cells and other pathogens. Rhodamine 6G (R6G) is a well-known laser dye with poor aqueous solubility, and lower sensitivity poses an issue in using PS for PDT. Nanocarrier systems are needed to deliver R6G to cancer targets since PDT requires a higher accumulation of PS. It was found that R6G-conjugated gold nanoparticles (AuNP) have a higher ROS quantum yield of 0.92 compared to 0.3 in an aqueous R6G solution, increasing their potency as PS. Cytotoxicity assessment on A549 cells and antibacterial assay on MDR Pseudomonas aeruginosa collected from a sewage treatment plant are the evidence to support efficient PDT. In addition to their enhanced quantum yields, the decorated particles are effective in generating fluorescent signals that can be used for cellular imaging and real-time optical imaging, and the presence of AuNP is a valuable addition to CT imaging. Furthermore, the fabricated particle exhibits anti-Stokes properties, which makes it suitable for use as a background-free biological imaging agent. As a result, R6G-conjugated AuNP is an effective theranostic agent that prevents the progression of cancer and MDR bacteria, along with contrasting abilities in medical imaging with minimal toxicity observed in in vitro and in vivo assays using zebrafish embryos.
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References
Zewde, N., Ria, F., & Rehani, M. M. (2022). Organ doses and cancer risk assessment in patients exposed to high doses from recurrent CT exams. European Journal of Radiology, 149, 110224.
Aly, S., Daniel, C. L., Bae, S., Scarinci, I. C., Hardy, C. M., Fouad, M. N., et al. (2021). Cancer-related beliefs and preventive health practices among residents of rural versus urban counties in Alabama rural/urban comparison of lifestyle beliefs and practices. Cancer Prevention Research, 14(5), 593–602.
Wu, X.-R. (2005). Urothelial tumorigenesis: A tale of divergent pathways. Nature Reviews. Cancer, 5(9), 713–725.
Elmore, L. W., Greer, S. F., Daniels, E. C., Saxe, C. C., Melner, M. H., Krawiec, G. M., et al. (2021). Blueprint for cancer research: Critical gaps and opportunities. CA: a Cancer Journal for Clinicians, 71(2), 107–139.
Abd-El-Azim, H., Tekko, I. A., Ali, A., Ramadan, A., Nafee, N., Khalafallah, N., et al. (2022). Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer. Journal of Controlled Release, 348, 849–869.
Vimaladevi, M., Divya, K. C., & Girigoswami, A. (2016). Liposomal nanoformulations of rhodamine for targeted photodynamic inactivation of multidrug resistant gram negative bacteria in sewage treatment plant. Journal of Photochemistry and Photobiology B: Biology, 162, 146–152.
Pallavi, P., Sharmiladevi, P., Haribabu, V., Girigoswami, K., & Girigoswami, A. (2022). A nano approach to formulate photosensitizers for photodynamic therapy. Current Nanoscience, 18(6), 675–689.
Pallavi, P., Girigoswami, A., Girigoswami, K., Hansda, S., & Ghosh, R. (2022). Photodynamic therapy in cancer. Handbook of Oxidative Stress in Cancer: Therapeutic Aspects, (pp. 1–24). Singapore: Springer Nature Singapore Pte Ltd. https://doi.org/10.1007/978-981-16-1247-3_232-1
Redmond, R. W., & Kochevar, I. E. (2006). Spatially resolved cellular responses to singlet oxygen. Photochemistry and Photobiology, 82(5), 1178–1186.
Rosenthal, I., & Ben-Hur, E. (1995). Role of oxygen in the phototoxicity of phthalocyanines. International Journal of Radiation Biology, 67(1), 85–91.
Bergamini, C. M., Gambetti, S., Dondi, A., & Cervellati, C. (2004). Oxygen, reactive oxygen species and tissue damage. Current Pharmaceutical Design, 10(14), 1611–1626.
Sobhani, N., & Samadani, A. A. (2021). Implications of photodynamic cancer therapy: An overview of PDT mechanisms basically and practically. Journal of the Egyptian National Cancer Institute, 33(1), 1–13.
Ding, H., Yu, H., Dong, Y., Tian, R., Huang, G., Boothman, D. A., et al. (2011). Photoactivation switch from type II to type I reactions by electron-rich micelles for improved photodynamic therapy of cancer cells under hypoxia. Journal of Controlled Release, 156(3), 276–280.
Wilson, B. C., & Patterson, M. S. (2008). The physics, biophysics and technology of photodynamic therapy. Physics in Medicine and Biology, 53(9), R61.
Li, X., Kwon, N., Guo, T., Liu, Z., & Yoon, J. (2018). Innovative strategies for hypoxic-tumor photodynamic therapy. Angewandte Chemie, International Edition, 57(36), 11522–11531.
Mfouo-Tynga, I. S., Dias, L. D., Inada, N. M., & Kurachi, C. (2021). Features of third generation photosensitizers used in anticancer photodynamic therapy. Photodiagnosis and Photodynamic Therapy, 34, 102091.
Correia-Barros, G., Serambeque, B., Carvalho, M. J., Marto, C. M., Pineiro, M., Pinho e Melo, T. M., et al. (2022). Applications of photodynamic therapy in endometrial diseases. Bioengineering., 9(5), 226.
Gunaydin, G., Gedik, M. E., & Ayan, S. (2021). Photodynamic therapy—Current limitations and novel approaches. Frontiers in Chemistry, 9, 691697.
Chen, D., Xu, Q., Wang, W., Shao, J., Huang, W., & Dong, X. (2021). Type I photosensitizers revitalizing photodynamic oncotherapy. Small, 17(31), 2006742.
Hung, H.-I. C. (2012). Mitochondrial iron uptake through mitoferrin2 sensitizes human head and neck squamous carcinoma cells to photodynamic therapy. Medical University of South Carolina.
Tsai, J. C., Chiang, C. P., Chen, H. M., Huang, S. B., Wang, C. W., Lee, M. I., et al. (2004). Photodynamic therapy of oral dysplasia with topical 5-aminolevulinic acid and light-emitting diode array. Lasers in Surgery and Medicine: The Official Journal of the American Society for Laser Medicine and Surgery, 34(1), 18–24.
Chatterjee, D. K., Fong, L. S., & Zhang, Y. (2008). Nanoparticles in photodynamic therapy: An emerging paradigm. Advanced Drug Delivery Reviews, 60(15), 1627–1637.
Li, L., & Huh, K. M. (2014). Polymeric nanocarrier systems for photodynamic therapy. Biomaterials Research, 18(1), 19.
Gibot, L., Lemelle, A., Till, U., Moukarzel, B., Mingotaud, A.-F., Pimienta, V., et al. (2014). Polymeric micelles encapsulating photosensitizer: Structure/photodynamic therapy efficiency relation. Biomacromolecules, 15(4), 1443–1455.
dos Santos, A. F., Arini, G. S., de Almeida, D. R. Q., & Labriola, L. (2021). Nanophotosensitizers for cancer therapy: A promising technology? Journal of Physics: Materials, 4(3), 032006.
Escudero, A., Carrillo-Carrión, C., Castillejos, M. C., Romero-Ben, E., Rosales-Barrios, C., & Khiar, N. (2021). Photodynamic therapy: Photosensitizers and nanostructures. Materials Chemistry Frontiers, 5(10), 3788–3812.
Vedakumari, W. S., Prabu, P., Babu, S. C., & Sastry, T. P. (2013). Fibrin nanoparticles as possible vehicles for drug delivery. Biochimica et Biophysica Acta (BBA) - General Subjects, 1830(8), 4244–4253.
Schiwon, K., Brauer, H.-D., Gerlach, B., Müller, C., & Montforts, F.-P. (1994). Potential photosensitizers for photodynamic therapy: IV. Photophysical and photochemical properties of azaporphyrin and azachlorin derivatives. Journal of Photochemistry and Photobiology B: Biology, 23(2-3), 239–243.
Shen, Y., Sun, Y., Yan, R., Chen, E., Wang, H., Ye, D., et al. (2017). Rational engineering of semiconductor QDs enabling remarkable 1O2 production for tumor-targeted photodynamic therapy. Biomaterials, 148, 31–40.
Castano, A. P., Demidova, T. N., & Hamblin, M. R. (2004). Mechanisms in photodynamic therapy: Part one—Photosensitizers, photochemistry and cellular localization. Photodiagnosis and Photodynamic Therapy, 1(4), 279–293.
Shigemitsu, H., Sato, K., Hagio, S., Tani, Y., Mori, T., Ohkubo, K., et al. (2022). Amphiphilic rhodamine nano-assembly as a type I supramolecular photosensitizer for photodynamic therapy. ACS Applied Nano Materials, 5(10), 14954–14960.
Zhou, L., Wei, F., Xiang, J., Li, H., Li, C., Zhang, P., et al. (2020). Enhancing the ROS generation ability of a rhodamine-decorated iridium (III) complex by ligand regulation for endoplasmic reticulum-targeted photodynamic therapy. Chemical Science, 11(44), 12212–12220.
Ghosh, D., Sarkar, D., Girigoswami, A., & Chattopadhyay, N. (2011). A fully standardized method of synthesis of gold nanoparticles of desired dimension in the range 15 nm–60 nm. Journal of Nanoscience and Nanotechnology, 11(2), 1141–1146.
Girigoswami, A., Li, T., Jung, C., Mun, H. Y., & Park, H. G. (2009). Gold nanoparticle-based label-free detection of BRCA1 mutations utilizing DNA ligation on DNA microarray. Journal of Nanoscience and Nanotechnology, 9(2), 1019–1024.
Mosinger, J., & Mička, Z. (1997). Quantum yields of singlet oxygen of metal complexes of meso-tetrakis (sulphonatophenyl) porphine. Journal of Photochemistry and Photobiology A: Chemistry, 107(1-3), 77–82.
Girigoswami, A., & Girigoswami, K. (2021). Size attenuated copper doped zirconia nanoparticles enhances in vitro antimicrobial properties. Europe PMC.
Metkar, S. K., Girigoswami, A., Bondage, D. D., Shinde, U. G., & Girigoswami, K. (2022). The potential of lumbrokinase and serratiopeptidase for the degradation of Aβ 1–42 peptide–an in vitro and in silico approach. The International Journal of Neuroscience, 1-12.
Baskić, D., Popović, S., Ristić, P., & Arsenijević, N. N. (2006). Analysis of cycloheximide-induced apoptosis in human leukocytes: Fluorescence microscopy using annexin V/propidium iodide versus acridin orange/ethidium bromide. Cell Biology International, 30(11), 924–932.
Haribabu, V., Girigoswami, K., & Girigoswami, A. (2021). Magneto-silver core–shell nanohybrids for theragnosis. Nano-Structures & Nano-Objects, 25, 100636.
Sharmiladevi, P., Akhtar, N., Haribabu, V., Girigoswami, K., Chattopadhyay, S., & Girigoswami, A. (2019). Excitation wavelength independent carbon-decorated ferrite nanodots for multimodal diagnosis and stimuli responsive therapy. ACS Applied Bio Materials, 2(4), 1634–1642.
Agraharam, G., Girigoswami, A., & Girigoswami, K. (2021). Nanoencapsulated myricetin to improve antioxidant activity and bioavailability: A study on zebrafish embryos. Chemistry (Easton), 4(1), 1–17.
Jin, R., Wu, G., Li, Z., Mirkin, C. A., & Schatz, G. C. (2003). What controls the melting properties of DNA-linked gold nanoparticle assemblies? Journal of the American Chemical Society, 125(6), 1643–1654.
Storhoff, J. J., Elghanian, R., Mucic, R. C., Mirkin, C. A., & Letsinger, R. L. (1998). One-pot colorimetric differentiation of polynucleotides with single base imperfections using gold nanoparticle probes. Journal of the American Chemical Society, 120(9), 1959–1964.
Baranyaiová, T., & Bujdák, J. (2016). Reaction kinetics of molecular aggregation of rhodamine 123 in colloids with synthetic saponite nanoparticles. Applied Clay Science, 134, 103–109.
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CARE is acknowledged for financial and infrastructural assistance. PP, KH, and PG are thankful to CARE for the fellowship.
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Pallavi, P., Harini, K., Crowder, S. et al. Rhodamine-Conjugated Anti-Stokes Gold Nanoparticles with Higher ROS Quantum Yield as Theranostic Probe to Arrest Cancer and MDR Bacteria. Appl Biochem Biotechnol 195, 6979–6993 (2023). https://doi.org/10.1007/s12010-023-04475-0
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DOI: https://doi.org/10.1007/s12010-023-04475-0