Skip to main content
SpringerLink
Log in

Gold cluster encapsulated liposomes: theranostic agent with stimulus triggered release capability

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Cancer is a major cause of death worldwide. Cancer-resistant to chemo or radiotherapy treatment is a challenge that could be overcome by a nanotechnology approach. Providing a theranostic nano-platform for different cancer treatment strategies could be revolutionary. Here we introduce a multifunctional theranostic nanostructure which has the capacity for improving cancer diagnosis and treatment through better chemo and radiotherapy and current x-ray imaging systems through co-encapsulation of a small gold cluster and anticancer drug doxorubicin. 2 nm gold clusters represent good heating under radio frequency electric field (RF-EF) exposure and have been used for in vitro hyperthermia treatment of cancerous cells. Liposomal doxorubicin (169 ± 19.8 nm) with gold clusters encapsulation efficiency of 13.2 ± 3.0% and doxorubicin encapsulation efficiency of 64.7 ± 0.7% were prepared and studied as a theranostic agent with a high potential in different cancer treatment modalities. Exposure to a radiofrequency electric field on prepared formulation caused 20.2 ± 2.1% drug release and twice decreasing of IC50 on colorectal carcinoma cells. X-ray attenuation efficiency of the liposomal gold cluster was better than commercial iohexol and free gold clusters in different concentrations. Finally, treatment of gold clusters on cancerous cells results in a significant decrease in the viability of irradiated cells to cobalt-60 beam. Based on these experiments, we concluded that the conventional liposomal formulation of doxorubicin that has been co-encapsulated with small gold clusters could be a suitable theranostic nanostructure for cancer treatment and merits further investigation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. DeAngelis LM, et al. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93–10. J Clin Oncol. 2002;20(24):4643–8.

    Article  PubMed  Google Scholar 

  2. Sriraman SK, Aryasomayajula B, Torchilin VP. Barriers to drug delivery in solid tumors. Tissue Barriers. 2014;2(3): e29528.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Fatemi F, et al. Construction of genetically engineered M13K07 helper phage for simultaneous phage display of gold binding peptide 1 and nuclear matrix protein 22 ScFv antibody. Colloids Surf B. 2017;159:770–80.

    Article  CAS  Google Scholar 

  4. Koosha F, et al. Mesoporous silica coated gold nanorods: a multifunctional theranostic platform for radiotherapy and X-ray imaging. J Porous Mater. 2021;28(6):1961–8.

    Article  CAS  Google Scholar 

  5. Neshastehriz A, et al. In-vitro investigation of green synthesized gold nanoparticle's role in combined photodynamic and radiation therapy of cancerous cells. Adv Nat Sci. 2020;11(4).

  6. Kamalabadi M, et al. Folate functionalized gold-coated magnetic nanoparticles effect in combined electroporation and radiation treatment of HPV-positive oropharyngeal cancer. Med Oncol. 2022;39(12).

  7. Baijal G, et al. Comparative study of one pot synthesis of PEGylated gold and silver nanoparticles for imaging and radiosensitization of oral cancers. Radiat Phys Chem. 2022;194: 109990.

    Article  Google Scholar 

  8. Lin M-H, et al. Comparison of organic and inorganic germanium compounds in cellular radiosensitivity and preparation of germanium nanoparticles as a radiosensitizer. Int J Radiat Biol. 2009;85(3):214–26.

    Article  CAS  PubMed  Google Scholar 

  9. Porcel E, et al. Platinum nanoparticles: a promising material for future cancer therapy? Nanotechnology. 2010;21(8): 085103.

    Article  Google Scholar 

  10. Shirkhanloo H, et al. Novel semisolid design based on bismuth oxide (Bi2O3) nanoparticles for radiation protection. Nanomed Res J. 2017;2(4):230–8.

    CAS  Google Scholar 

  11. Chithrani DB, et al. Gold nanoparticles as radiation sensitizers in cancer therapy. Radiat Res. 2010;173(6):719–28.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang X-D, et al. In vivo renal clearance, biodistribution, toxicity of gold nanoclusters. Biomaterials. 2012;33(18):4628–38.

    Article  CAS  PubMed  Google Scholar 

  13. Khlebtsov N, Dykman L. Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies. Chem Soc Rev. 2011;40(3):1647–71.

    Article  CAS  PubMed  Google Scholar 

  14. Hirn S, et al. Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration. Eur J Pharm Biopharm. 2011;77(3):407–16.

    Article  CAS  PubMed  Google Scholar 

  15. Drummond DC, et al. Pharmacokinetics and in vivo drug release rates in liposomal nanocarrier development. J Pharm Sci. 2008;97(11):4696–740.

    Article  CAS  PubMed  Google Scholar 

  16. Drummond DC, et al. Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol Rev. 1999;51(4):691–744.

    CAS  PubMed  Google Scholar 

  17. Halm U, et al. A phase II study of pegylated liposomal doxorubicin for treatment of advanced hepatocellular carcinoma. Ann Oncol. 2000;11(1):113–4.

    Article  CAS  PubMed  Google Scholar 

  18. Chidiac T, et al. Phase II trial of liposomal doxorubicin (Doxil®) in advanced soft tissue sarcomas. Invest New Drugs. 2000;18(3):253–9.

    Article  CAS  PubMed  Google Scholar 

  19. Laginha KM, et al. Determination of doxorubicin levels in whole tumor and tumor nuclei in murine breast cancer tumors. Clin Cancer Res. 2005;11(19):6944–9.

    Article  CAS  PubMed  Google Scholar 

  20. Tseng Y-L, Liu J-J, Hong R-L. Translocation of liposomes into cancer cells by cell-penetrating peptides penetratin and tat: a kinetic and efficacy study. Mol Pharmacol. 2002;62(4):864–72.

    Article  CAS  PubMed  Google Scholar 

  21. Ng K-Y, et al. The effects of polyethyleneglycol (PEG)-derived lipid on the activity of target-sensitive immunoliposome. Int J Pharm. 2000;193(2):157–66.

    Article  CAS  PubMed  Google Scholar 

  22. Parr MJ, et al. Accumulation of liposomal lipid and encapsulated doxorubicin in murine Lewis lung carcinoma: the lack of beneficial effects by coating liposomes with poly (ethylene glycol). J Pharmacol Exp Ther. 1997;280(3):1319–27.

    CAS  PubMed  Google Scholar 

  23. Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013;65(1):36–48.

    Article  CAS  PubMed  Google Scholar 

  24. Biabangard A, et al. Study of FA12 peptide-modified PEGylated liposomal doxorubicin (PLD) as an effective ligand to target Muc1 in mice bearing C26 colon carcinoma: in silico, in vitro, and in vivo study. Expert Opin Drug Deliv. 2022;19(12):1710–24.

    Article  CAS  PubMed  Google Scholar 

  25. Bibi S, et al. Trigger release liposome systems: local and remote controlled delivery? J Microencapsul. 2012;29(3):262–76.

    Article  CAS  PubMed  Google Scholar 

  26. Amini SM, Kharrazi S, Jaafari MR. Radio frequency hyperthermia of cancerous cells with gold nanoclusters: an in vitro investigation. Gold Bull. 2017;50(1):43–50.

    Article  CAS  Google Scholar 

  27. Amin M, Badiee A, Jaafari MR. Improvement of pharmacokinetic and antitumor activity of PEGylated liposomal doxorubicin by targeting with N-methylated cyclic RGD peptide in mice bearing C-26 colon carcinomas. Int J Pharm. 2013;458(2):324–33.

    Article  CAS  PubMed  Google Scholar 

  28. Bartlett GR. Phosphorus assay in column chromatography. J Biol Chem. 1959;234:466–8.

    Article  CAS  PubMed  Google Scholar 

  29. Bolotin EM, et al. Ammonium sulfate gradients for efficient and stable remote loading of amphipathic weak bases into liposomes and ligandoliposomes. J Liposome Res. 1994;4(1):455–79.

    Article  Google Scholar 

  30. Haran G, et al. Transmembrane ammonium sulfate gradients in liposomes produce efficient and stable entrapment of amphipathic weak bases. Biochim Biophys Acta. 1993;1151(2):201–15.

    Article  CAS  PubMed  Google Scholar 

  31. Huang Z, Jaafari MR, Szoka FC Jr. Disterolphospholipids: nonexchangeable lipids and their application to liposomal drug delivery. Angew Chem. 2009;121(23):4210–3.

    Article  Google Scholar 

  32. Siegel MJ, et al. Radiation dose and image quality in pediatric CT: effect of technical factors and phantom size and shape 1. Radiology. 2004;233(2):515–22.

    Article  PubMed  Google Scholar 

  33. Pradhan P, et al. Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy. J Control Release. 2010;142(1):108–21.

    Article  CAS  PubMed  Google Scholar 

  34. Lorenzato C, et al. MRI contrast variation of thermosensitive magnetoliposomes triggered by focused ultrasound: a tool for image-guided local drug delivery. Contrast Media Mol Imaging. 2013;8(2):185–92.

    Article  CAS  PubMed  Google Scholar 

  35. Zarchi AAK, et al. Synthesis and characterisation of liposomal doxorubicin with loaded gold nanoparticles. IET Nanobiotechnol. 2018;12:846–9.

    Article  Google Scholar 

  36. Mathiyazhakan M, et al. Non-invasive controlled release from gold nanoparticle integrated photo-responsive liposomes through pulse laser induced microbubble cavitation. Colloids Surf B. 2015;126:569–74.

    Article  CAS  Google Scholar 

  37. Xia Y, et al. Construction of thermal-and light-responsive liposomes noncovalently decorated with gold nanoparticles. RSC Adv. 2014;4(84):44568–74.

    Article  CAS  Google Scholar 

  38. Demir B, et al. Gold nanoparticle loaded phytosomal systems: synthesis, characterization and in vitro investigations. RSC Adv. 2014;4(65):34687–95.

    Article  CAS  Google Scholar 

  39. Freeny PC, et al. Colorectal carcinoma evaluation with CT: preoperative staging and detection of postoperative recurrence. Radiology. 1986;158(2):347–53.

    Article  CAS  PubMed  Google Scholar 

  40. Rifkin MD, Ehrlich S, Marks G. Staging of rectal carcinoma: prospective comparison of endorectal US and CT. Radiology. 1989;170(2):319–22.

    Article  CAS  PubMed  Google Scholar 

  41. Lusic H, Grinstaff MW. X-ray-computed tomography contrast agents. Chem Rev. 2012;113(3):1641–66.

    Article  PubMed  Google Scholar 

  42. Hainfeld, J., et al. Gold nanoparticles: a new X-ray contrast agent. Br J Radiol 2014.

  43. Rabin O, et al. An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat Mater. 2006;5(2):118–22.

    Article  CAS  PubMed  Google Scholar 

  44. Kandanapitiye MS, et al. Synthesis, characterization, and X-ray attenuation properties of ultrasmall BiOI nanoparticles: toward renal clearable particulate CT contrast agents. Inorg Chem. 2014;53(19):10189–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Liu Z, et al. Long-circulating Er 3+-doped Yb 2 O 3 up-conversion nanoparticle as an in vivo X-Ray CT imaging contrast agent. Biomaterials. 2012;33(28):6748–57.

    Article  CAS  PubMed  Google Scholar 

  46. Liu Y, et al. A high-performance ytterbium-based nanoparticulate contrast agent for in vivo X-ray computed tomography imaging. Angew Chem Int Ed. 2012;51(6):1437–42.

    Article  CAS  Google Scholar 

  47. Lechtman E, et al. Implications on clinical scenario of gold nanoparticle radiosensitization in regards to photon energy, nanoparticle size, concentration and location. Phys Med Biol. 2011;56(15):4631.

    Article  CAS  PubMed  Google Scholar 

  48. Khoshgard K, et al. Radiosensitization effect of folate-conjugated gold nanoparticles on HeLa cancer cells under orthovoltage superficial radiotherapy techniques. Phys Med Biol. 2014;59(9):2249.

    Article  PubMed  Google Scholar 

  49. Hainfeld JF, et al. Radiotherapy enhancement with gold nanoparticles. J Pharm Pharmacol. 2008;60(8):977–85.

    Article  CAS  PubMed  Google Scholar 

  50. Leung MK, et al. Irradiation of gold nanoparticles by x-rays: Monte Carlo simulation of dose enhancements and the spatial properties of the secondary electrons production. Med Phys. 2011;38(2):624–31.

    Article  CAS  PubMed  Google Scholar 

  51. Hill R, et al. Advances in kilovoltage X-ray beam dosimetry. Phys Med Biol. 2014;59(6):R183.

    Article  PubMed  Google Scholar 

  52. Goodman CM, et al. Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. Bioconjug Chem. 2004;15(4):897–900.

    Article  CAS  PubMed  Google Scholar 

  53. Marquis BJ, et al. Analytical methods to assess nanoparticle toxicity. Analyst. 2009;134(3):425–39.

    Article  CAS  PubMed  Google Scholar 

  54. Niidome T, et al. PEG-modified gold nanorods with a stealth character for in vivo applications. J Control Release. 2006;114(3):343–7.

    Article  CAS  PubMed  Google Scholar 

  55. Mathew A, Pradeep T. Noble metal clusters: applications in energy, environment, and biology. Part Part Syst Charact. 2014;31(10):1017–53.

    Article  CAS  Google Scholar 

  56. Mayer L, Bally M, Cullis P. Uptake of adriamycin into large unilamellar vesicles in response to a pH gradient. Biochim Biophys Acta. 1986;857(1):123–6.

    Article  CAS  PubMed  Google Scholar 

  57. Hanson GW, Monreal R, Apell SP. Electromagnetic absorption mechanisms in metal nanospheres: Bulk and surface effects in radiofrequency-terahertz heating of nanoparticles. J Appl Phys. 2011;109(12): 124306.

    Article  Google Scholar 

Download references

Acknowledgements

This work has been funded by the Tehran University of Medical Sciences (93-01-87-25211). The authors are grateful to Dr. Hossein Ghadiri for providing the scanning holder for computed tomography experiments.

Funding

Funding was provided by Tehran University of Medical Sciences and Health Services.

Author information

Authors and Affiliations

  1. Radiation Biology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran

    Seyed Mohammad Amini

  2. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine (SATiM), Tehran University of Medical Sciences (TUMS), Tehran, Iran

    Seyed Mohammad Amini, Seyed Mahdi Rezayat & Sharmin Kharrazi

  3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Mahdi Rezayat

  4. Nanotechnology Research Centre, Novel Drug Delivery Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Rassoul Dinarvand

  5. Pharmaceutical Technology Institute, School of Pharmacy, Nanotechnology Research Center, Mashhad University of Medical Sciences, 91775-1365, Mashhad, Iran

    Mahmoud Reza Jaafari

  6. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, 91775-1365, Mashhad, Iran

    Mahmoud Reza Jaafari

Authors
  1. Seyed Mohammad Amini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seyed Mahdi Rezayat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rassoul Dinarvand
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sharmin Kharrazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mahmoud Reza Jaafari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Sharmin Kharrazi or Mahmoud Reza Jaafari.

Ethics declarations

Conflict of interest

None.

Additional information

Publisher's Note

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

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

Amini, S.M., Rezayat, S.M., Dinarvand, R. et al. Gold cluster encapsulated liposomes: theranostic agent with stimulus triggered release capability. Med Oncol 40, 126 (2023). https://doi.org/10.1007/s12032-023-01991-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-023-01991-1

Keywords

Search

Navigation