Skip to main content
Log in

Rhodamine-Conjugated Anti-Stokes Gold Nanoparticles with Higher ROS Quantum Yield as Theranostic Probe to Arrest Cancer and MDR Bacteria

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

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.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2.
Fig. 3
Fig. 4
Fig. 5
Fig. 6:

Similar content being viewed by others

Data Availability

The authors confirm that the data supporting the findings of this study are available within the article and/or its supplementary material.

References

  1. 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.

    Article  PubMed  Google Scholar 

  2. 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.

    Article  PubMed  Google Scholar 

  3. Wu, X.-R. (2005). Urothelial tumorigenesis: A tale of divergent pathways. Nature Reviews. Cancer, 5(9), 713–725.

    Article  PubMed  CAS  Google Scholar 

  4. 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.

    PubMed  Google Scholar 

  5. 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.

    Article  PubMed  CAS  Google Scholar 

  6. 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.

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  CAS  Google Scholar 

  8. 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

  9. Redmond, R. W., & Kochevar, I. E. (2006). Spatially resolved cellular responses to singlet oxygen. Photochemistry and Photobiology, 82(5), 1178–1186.

    Article  PubMed  CAS  Google Scholar 

  10. Rosenthal, I., & Ben-Hur, E. (1995). Role of oxygen in the phototoxicity of phthalocyanines. International Journal of Radiation Biology, 67(1), 85–91.

    Article  PubMed  CAS  Google Scholar 

  11. Bergamini, C. M., Gambetti, S., Dondi, A., & Cervellati, C. (2004). Oxygen, reactive oxygen species and tissue damage. Current Pharmaceutical Design, 10(14), 1611–1626.

    Article  PubMed  CAS  Google Scholar 

  12. 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.

    Article  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Wilson, B. C., & Patterson, M. S. (2008). The physics, biophysics and technology of photodynamic therapy. Physics in Medicine and Biology, 53(9), R61.

    Article  PubMed  CAS  Google Scholar 

  15. 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.

    Article  PubMed  CAS  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Gunaydin, G., Gedik, M. E., & Ayan, S. (2021). Photodynamic therapy—Current limitations and novel approaches. Frontiers in Chemistry, 9, 691697.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Chen, D., Xu, Q., Wang, W., Shao, J., Huang, W., & Dong, X. (2021). Type I photosensitizers revitalizing photodynamic oncotherapy. Small, 17(31), 2006742.

    Article  CAS  Google Scholar 

  20. 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.

    Google Scholar 

  21. 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.

    Article  Google Scholar 

  22. Chatterjee, D. K., Fong, L. S., & Zhang, Y. (2008). Nanoparticles in photodynamic therapy: An emerging paradigm. Advanced Drug Delivery Reviews, 60(15), 1627–1637.

    Article  PubMed  CAS  Google Scholar 

  23. Li, L., & Huh, K. M. (2014). Polymeric nanocarrier systems for photodynamic therapy. Biomaterials Research, 18(1), 19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. 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.

    Article  PubMed  CAS  Google Scholar 

  25. 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.

    Google Scholar 

  26. 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.

    Article  CAS  Google Scholar 

  27. 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.

    Article  PubMed  CAS  Google Scholar 

  28. 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.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    Article  PubMed  CAS  Google Scholar 

  30. 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. 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.

    Article  CAS  Google Scholar 

  32. 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. 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.

    Article  PubMed  CAS  Google Scholar 

  34. 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.

    Article  PubMed  CAS  Google Scholar 

  35. 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.

    Article  CAS  Google Scholar 

  36. Girigoswami, A., & Girigoswami, K. (2021). Size attenuated copper doped zirconia nanoparticles enhances in vitro antimicrobial properties. Europe PMC.

    Google Scholar 

  37. 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.

  38. 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.

    Article  PubMed  Google Scholar 

  39. Haribabu, V., Girigoswami, K., & Girigoswami, A. (2021). Magneto-silver core–shell nanohybrids for theragnosis. Nano-Structures & Nano-Objects, 25, 100636.

    Article  CAS  Google Scholar 

  40. 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.

    Article  PubMed  CAS  Google Scholar 

  41. 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.

    Google Scholar 

  42. 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.

    Article  PubMed  CAS  Google Scholar 

  43. 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.

    Article  CAS  Google Scholar 

  44. 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.

    Article  Google Scholar 

Download references

Acknowledgements

CARE is acknowledged for financial and infrastructural assistance. PP, KH, and PG are thankful to CARE for the fellowship.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Agnishwar Girigoswami.

Ethics declarations

Ethics Approval

All work has been done under the guidelines of the Institutional Ethics Committee.

Consent to Participate

All authors have their consent to participate.

Consent for Publication

All authors have their consent to publish their work.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1:

Supplementary Data (DOCX 2380 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-023-04475-0

Keywords

Navigation