Skip to main content
Log in

Calcium carbonate microparticles containing a photosensitizer photosens: Preparation, ultrasound stimulated dye release, and in vivo application

  • Published:
Nanotechnologies in Russia Aims and scope Submit manuscript

Abstract

Calcium carbonate microparticles with a size of 0.9 ± 0.2 μm containing a photosensitizer Photosens in a concentration of 2.0 ± 0.2 wt % were prepared by ultrasound-stimulated coprecipitation (20 kHz, 1W/cm2). It is shown that the encapsulated photosensitizer can be released by ultrasonic irradiation (0.89MHz, 1 W/cm2, 5 min) as a result of the destruction and recrystallization of calcium carbonate micro-particles. It is established that the combined ultrasonic (0.89 MHz, 1 W/cm2) and light (670 nm, 10 mW/cm2) in vivo influence on the transferred PC-1 strain tumors of rat liver containing intratumorally injected micro-containers with a photosensitizer gives rise to dystrophic changes in tumor cells and to the appearance of extensive necrotic centers, pointing to the presence of the evident destructive effect. Such microcontainers are proposed for use in treating external tumors or tumors accessible for ultrasonic and optical irradiation.

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.

Similar content being viewed by others

References

  1. T. J. Dougherty, “Photodynamic therapy-new approaches,” Seminars Surg. Oncol. 5(1), 6–16 (1989).

    Article  Google Scholar 

  2. E. A. Lukyanets, “Phthalocyanines as photosensitizers in the photodynamic therapy of cancer,” J. Porphyrins Phthalocyanines 3(6), 424–432 (1999).

    Article  Google Scholar 

  3. M. DeRosa and R. Crutchley, “Photosensitized singlet oxygen and its applications,” Coord. Chem. Rev. 233–234, 351–371 (2002).

    Article  Google Scholar 

  4. E. F. Stranadko, “The main stages of development and state of the art of photodynamical therapy in Russia,” Lazer. Med. 16(2), 4–14 (2012).

    Google Scholar 

  5. M. Gel’fond, “Photodynamical therapy in oncology,” Prakt. Onkol. 8(4), 204–210 (2007).

    Google Scholar 

  6. C. Hopper, “Photodynamic therapy: a clinical reality in the treatment of cancer,” Lancet Oncol. 1, 212–219 (2000).

    Article  Google Scholar 

  7. M. Jin, B. Yang, W. Zhang, and Y. Wang, “Photodynamic therapy for upper gastrointestinal tumours over the past 10 years,” Seminars Surg. Oncol. 10(2), 111–113 (1994).

    Article  Google Scholar 

  8. N.-Z. Zhang, Y. Zhu, W. Pan, W.-Q. Ma, and A.-L. Shao, “Photodynamic therapy combined with local chemotherapy for the treatment of advanced esophagocardiac carcinoma,” Photodiagn. Photodynam. Therapy 4(1), 60–64 (2007).

    Article  Google Scholar 

  9. A. Radu, P. Grosjean, Y. Jaquet, R. Pilloud, G. Wagnieres, H. van den Bergh, and P. Monnier, “Photodynamic therapy and endoscopic mucosal resection as minimally invasive approaches for the treatment of early esophageal tumors: pre-clinical and clinical experience in Lausanne,” Photodiagn. Photodynam. Therapy 2(1), 35–44 (2005).

    Article  Google Scholar 

  10. B. F. Overholt, K. K. Wang, J. S. Burdick, C. J. Lightdale, M. Kimmey, H. R. Nava, M. V. Sivak, Jr., N. Nishioka, H. Barr, N. Marcon, M. Pedrosa, M. P. Bronner, M. Grace, and M. Depot, “Five-year efficacy and safety of photodynamic therapy with photofrin in Barrett’s high-grade dysplasia,” Gastrointest. Endoscopy 66(3), 460–468 (2007).

    Article  Google Scholar 

  11. J. P. Tardivo, A. Del Giglio, C. S. de Oliveira, D. S. Gabrielli, H. C. Junqueira, D. B. Tada, D. Severino, R. F. Turchiello, and M. S. Baptista, “Methylene blue in photodynamic therapy: from basic mechanisms to clinical applications,” Photodiagn. Photodynam. Therapy 2(3), 175–191 (2005).

    Article  Google Scholar 

  12. H. Kato, M. Harada, S. Ichinose, J. Usuda, T. Tsuchida, and T. Okunaka, “Photodynamic therapy (PDT) of lung cancer: experience of the Tokyo Medical University,” Photodiagn. Photodynam. Therapy 1(1), 49–55 (2004).

    Article  Google Scholar 

  13. V. I. Polsachev, A. E. Zykov, E. K. Slovokhodov, R. V. Basanov, A. B. Smirnov, and V. I. Ivanova-Radkevich, “Photodynamical therapy for gynecological patients with uterine neck pretumor pathology,” Khirurg, No. 7, 19 (2011).

    Google Scholar 

  14. K. Konopka and T. Goslinski, “Photodynamic therapy in dentistry,” J. Dental Res. 86(8), 694–707 (2007).

    Article  Google Scholar 

  15. C. Morton, K. E. McKenna, and L. E. Rhodes, “Guidelines for topical photodynamic therapy: update,” Brit. J. Dermatol. 159(6), 1245–1266 (2008).

    Article  Google Scholar 

  16. G. Jori, C. Fabris, M. Soncin, S. Ferro, O. Coppellotti, D. Dei, L. Fantetti, G. Chiti, and G. Roncucci, “Photodynamic therapy in the treatment of microbial infections: basic principles and perspective applications,” Lasers Surgery Med. 38(5), 468–481 (2006).

    Article  Google Scholar 

  17. D. Mitton and R. Ackroyd, “A brief overview of photo-dynamic therapy in Europe,” Photodiagn. Photodynam. Therapy 5(2), 103–111 (2008).

    Article  Google Scholar 

  18. S. H. Ibbotson, “An overview of topical photodynamic therapy in dermatology,” Photodiagn. Photodynam. Therapy 7(1), 16–23 (2010).

    Article  Google Scholar 

  19. Z. Huang, “An update on the regulatory status of PDT photosensitizers in China,” Photodiagn. Photodynam. Therapy 5(4), 285–287 (2008).

    Article  Google Scholar 

  20. A. Siero and S. Kwiatek, “Twenty years of experience with PDD and PDT in Poland-review,” Photodiagn. Photodynam. Therapy 6(2), 73–78 (2009).

    Article  Google Scholar 

  21. R. R. Allison, “Future PDT,” Photodiagn. Photodynam. Therapy 6(3–4), 231–234 (2009).

    Article  Google Scholar 

  22. Z. Huang, “Photodynamic therapy in China: over 25 years of unique clinical experience,” Photodiagn. Photodynam. Therapy 3(2), 71–84 (2006).

    Article  Google Scholar 

  23. A. P. Castano, T. N. Demidova, and M. R. Hamblin, “Mechanisms in photodynamic therapy: part one—photosensitizers, photochemistry and cellular localization,” Photodiagn. Photodynam. Therapy 1(4), 279–293 (2004).

    Article  Google Scholar 

  24. M. V. Budzinskaya, S. A. Shevchik, T. N. Kiseleva, V. B. Loshchenov, I. V. Gurova, I. V. Shchegoleva, S. G. Kuz’min, and G. N. Vorozhtsov, “The role of fluorescence diagnostics by using photoscence for patients with subretinal neovascular membrane,” Vestn. Oftal’mol. 123(6), 11–16 (2007).

    Google Scholar 

  25. S. A. Shevchik, M. V. Loshchenov, G. A. Meerovich, M. V. Budzinskaya, N. A. Ermakova, S. S. Kharnas, and V. B. Loshchenov, “A device for fluorescence diagnostics and photodynamical therapy for ophthalmopathy by using “Fotosens” drug,” Vestn. Oftal’mol. 121(5), 26–28 (2005).

    Google Scholar 

  26. N. Solban, I. Rizvi, and T. Hasan, “Targeted photodynamic therapy,” Lasers Surg. Med. 38(5), 522–531 (2006).

    Article  Google Scholar 

  27. W. Sharman, “Targeted photodynamic therapy via receptor mediated delivery systems,” Adv. Drug Delivery Rev. 56(1), 53–76 (2004).

    Article  Google Scholar 

  28. A. S. L. Derycke and P. A. M. De Witte, “Liposomes for photodynamic therapy,” Adv. Drug Delivery Rev. 56(1), 17–30 (2004).

    Article  Google Scholar 

  29. C. F. Van Nostrum, “Polymeric micelles to deliver photosensitizers for photodynamic therapy,” Adv. Drug Delivery Rev. 56(1), 9–16 (2004).

    Article  Google Scholar 

  30. M. E. Wieder, D. C. Hone, M. J. Cook, M. M. Handsley, J. Gavrilovic, and D. A. Russell, “Intracellular photodynamic therapy with photosensitizer-nanoparticle conjugates: cancer therapy using a “Trojan Horse”,” Photochem. Photobiol. Sci. 5(8), 727–734 (2006).

    Article  Google Scholar 

  31. A. Master, M. Livingston, and A. Sen Gupta, “Photodynamic nanomedicine in the treatment of solid tumors: perspectives and challenges,” J. Control. Release 168(1), 88–102 (2013).

    Article  Google Scholar 

  32. H. Eshghi, A. Sazgarnia, M. Rahimizadeh, N. Attaran, M. Bakavoli, and S. Soudmand, “Protoporphyrin IX-gold nanoparticle conjugates as an efficient photo-sensitizer in cervical cancer therapy,” Photodiagn. Photodynam. Therapy 10(3), 304–312 (2013).

    Article  Google Scholar 

  33. J. Schwiertz, A. Wiehe, S. Gräfe, B. Gitter, and M. Epple, “Calcium phosphate nanoparticles as efficient carriers for photodynamic therapy against cells and bacteria,” Biomaterials 30(19), 3324–3331 (2009).

    Article  Google Scholar 

  34. J. Klesing, A. Wiehe, B. Gitter, S. Gräfe, and M. Epple, “Positively charged calcium phosphate/polymer nanoparticles for photodynamic therapy,” J. Mater. Sci.: Mater. Med. 21(3), 887–892 (2010).

    Article  Google Scholar 

  35. T. Y. Ohulchanskyy, I. Roy, L. N. Goswami, Y. Chen, E.J. Berge, R. K. Pandey, A. R. Oseroff, and P. N. Prasad, “Organically modified silica nanoparticles with covalently incorporated photosensitizer for photodynamic therapy of cancer,” Nano Lett. 7(9), 2835–2842 (2007).

    Article  Google Scholar 

  36. S. Kim, T. Y. Ohulchanskyy, H. E. Pudavar, R. K. Pandey, and P. N. Prasad, “Organically modified silica nanoparticles co-encapsulating photosensitizing drug and aggregation-enhanced two-photon absorbing fluorescent dye aggregates for two-photon photodynamic therapy,” J. Amer. Chem. Soc. 129(9), 2669–2675 (2007).

    Article  Google Scholar 

  37. J. Qian, D. Wang, F. Cai, Q. Zhan, Y. Wang, and S. He, “Photosensitizer encapsulated organically modified silica nanoparticles for direct two-photon photodynamic therapy and in vivo functional imaging,” Biomaterials 33(19), 4851–4860 (2012).

    Article  Google Scholar 

  38. Y. Svenskaya, B. Parakhonskiy, A. Haase, V. Atkin, E. Lukyanets, D. Gorin, and R. Antolini, “Anticancer drug delivery system based on calcium carbonate particles loaded with a photosensitizers,” Biophys. Chem. 182, 11–15 (2013).

    Article  Google Scholar 

  39. D. V. Volodkin, N. I. Larionova, and G. B. Sukhorukov, “Protein encapsulation via porous CaCO3 microparticles templating,” Biomacromolecules 5(5), 1962–1972 (2004).

    Article  Google Scholar 

  40. A. I. Petrov, D. V. Volodkin, and G. B. Sukhorukov, “Protein-calcium carbonate coprecipitation: a tool for protein encapsulation,” Biotechn. Progr. 21(3), 918–925 (2005).

    Article  Google Scholar 

  41. B. V. Parakhonskiy, A. Haase, and R. Antolini, “Submicrometer vaterite containers: synthesis, substance loading, and release,” Angew. Chem. (Int. Ed. Engl.) 51(5), 1195–1197 (2012).

    Article  Google Scholar 

  42. B. Parakhonskiy, F. Tessarolo, A. Haase, and R. Antolini, “Dependence of sub-micron vaterite container release properties on pH and ionic strength of the surrounding solution,” Adv. Sci. Technol. (Faenza, Italy) 86, 81–85 (2012).

    Article  Google Scholar 

  43. C. Peng, Q. Zhao, and C. Gao, “Sustained delivery of doxorubicin by porous CaCO3 and chitosan/alginate multilayers-coated CaCO3 microparticles,” Colloids Surf. A: Physicochem. Eng. Aspects 353(2–3), 132–139 (2010).

    Article  Google Scholar 

  44. B. V. Parakhonskiy, C. Foss, E. Carletti, M. Fedel, A. Haase, A. Motta, C. Migliaresi, and R. Antolini, “Tailored intracellular delivery via a crystal phase transition in 400 nm vaterite particles,” Biomater. Sci. 1(12), 1273–1281 (2013).

    Article  Google Scholar 

  45. D. V. Volodkin, A. I. Petrov, M. Prevot, and G. B. Sukhorukov, “Matrix polyelectrolyte microcapsules: new system for macromolecule encapsulation,” Langmuir 20(8), 3398–3406 (2004).

    Article  Google Scholar 

  46. N. V. Andronova, E. M. Treshchalina, D. V. Filonenko, A. L. Nikolaev, and A. V. Gopin, “Combined therapy of malignant tumors by using local ultrasonic impact (experimental research),” Ross. Bioterapevt. Zh. 4(3), 101–105 (2005).

    Google Scholar 

  47. N. S. Sergeeva, I. K. Sviridova, A. L. Nikolaev, E. G. Ambrozevich, R. K. Kabisov, O. S. Sarantseva, O. A. Kurilyak, S. V. Alkov, and V. V. Sokolov, “Effects of various modes of sonication with low frequency ultrasound on in vitro survival of human tumor cells,” Bull. Experim. Biol. Med. 131(3), 279–282 (2001).

    Google Scholar 

  48. N. Yumita, K. Sasaki, and S. Umemura, “Sonodynamically induced antitumor effect of gallium-porphyrin complex by focused ultrasound on experimental kidney tumor,” Cancer Lett. 112, 79–86 (1997).

    Article  Google Scholar 

  49. N. V. Andronova, E. M. Treshchalina, D. V. Filonenko, A. L. Nikolaev, and A. V. Gopin, “Experimental approaches to combined tumors therapy by using sonodynamical ultrasound impact,” Ross. Bioterapevt. Zh. 3(2), 12 (2004).

    Google Scholar 

  50. N. V. Andronova, A. L. Nikolaev, S. V. Abramov, E. M. Treshchalina, D. S. Chicherin, G. K. Gerasimova, and O. L. Kaliya, “Efficiency of local ultrasound impact onto tumor by using USDT jointly with Teraftal and other sonosensibilizers,” Ross. Bioterapevt. Zh. 2(1), 12a–13 (2003).

    Google Scholar 

  51. J. Wang, L. Liu, B. Liu, Y. Guo, Y. Zhang, R. Xu, S. Wang, and X. Zhang, “Spectroscopic study on interaction of bovine serum albumin with sodium magnesium chlorophyllin and its sonodynamic damage under ultrasonic irradiation,” Spectrochim. Acta. Part A: Molec. Biomolec. Spectrosc. 75(1), 366–374 (2010).

    Article  Google Scholar 

  52. Z. H. Jin, N. Miyoshi, K. Ishiguro, S. Umemura, K. Kawabata, N. Yumita, I. Sakata, K. Takaoka, T. Udagawa, S. Nakajima, H. Tajiri, K. Ueda, M. Fukuda, and M. Kumakiri, “Combination effect of photodynamic and sonodynamic therapy on experimental skin squamous cell carcinoma in C3H/HeN mice,” J. Dermatol. 27(5), 294 (2000).

    Google Scholar 

  53. H. Kolarova, R. Bajgar, K. Tomankova, E. Krestyn, L. Dolezal, and J. Halek, “In vitro study of reactive oxygen species production during photodynamic therapy in ultrasound-pretreated cancer cells,” Physiol. Res. 56, 27–32 (2007).

    Google Scholar 

  54. H. Kolarova, K. Tomankova, R. Bajgar, P. Kolar, and R. Kubinek, “Photodynamic and Sonodynamic Treatment by Phthalocyanine on Cancer Cell Lines,” Ultrasound Med. Biol. 35(8), 1397–1404 (2009).

    Article  Google Scholar 

  55. D. A. Tserkovskii, E. N. Aleksandrova, T. P. Laptsevich, and Yu. P. Istomin, “Joint inertial photodynamical and sonodynamical therapy with Fotolon in vivo,” Ross. Bioterapevt. Zh. 12(2), 88 (2013).

    Google Scholar 

  56. Yu. V. Pavlov, Yu. A. Abli, and L. V. Uspenskii, “Joint application of low-frequency ultrasound and photodynamical therapy for prevention acute postoperative pleural empyema,” Khirurgiya, No. 4, 14–16 (2001).

    Google Scholar 

  57. A. L. Nikolaev, A. V. Gopin, V. E. Bozhevol’nov, E. M. Treshchalina, N. V. Andronova, and I. V. Melikhov, “Use of solid-phase inhomogeneities to increase the efficiency of ultrasonic therapy of oncological diseases,” Acoust. Phys. 55(4–5), 575 (2009).

    Article  Google Scholar 

  58. O. I. Trushina, E. G. Novikova, V. V. Sokolov, E. V. Filonenko, V. I. Chissov, and G. N. Vorozhtsov, “Photodynamic therapy of virus-associated precancer and early stages cancer of cervix uteri,” Photodiagn. Photodynam. Therapy 5(4), 256–259 (2008).

    Article  Google Scholar 

  59. R. R. Allison and C. H. Sibata, “Oncologic photodynamic therapy photosensitizers: a clinical review,” Photodiagn. Photodynam. Therapy 7(2), 61–75 (2010).

    Article  Google Scholar 

  60. M. V. Budzinskaya, S. A. Shevchik, V. G. Likhvantseva, V. B. Loshchenov, M. Taraz, S. G. Kuz’min, and G. N. Vorozhtsov, “Fluorescence diagnostics and photodynamical therapy by using Fotosens drug against epibulbar melanoma in the experiment,” Ross. Bioterapevt. Zh. 3(4), 24–28 (2004).

    Google Scholar 

  61. L. V. Uspenskii, L. V. Chistov, E. A. Kogan, V. B. Loshchenov, I. A. Ablitsov, V. K. Rybin, V. I. Zavodnov, D. I. Shiktorov, N. F. Serbinenko, and I. G. Semenova, “Endobronchial laser therapy in complex preoperative preparation of patients with lung diseases,” Khirurgiia, No. 2, 38–40 (2000).

    Google Scholar 

  62. E. F. Stranadko, M. I. Garbuzov, V. G. Zenger, A. N. Nasedkin, N. A. Markichev, M. V. Riabov, and I. V. Leskov, “Photodynamic therapy of recurrent and residual oropharyngeal and laryngeal tumors,” Vestn. Otorinolaringol. 38(3), 36–39 (2001).

    Google Scholar 

  63. E. V. Filonenko, V. V. Sokolov, V. I. Chissov, E. A. Lukyanets, and G. N. Vorozhtsov, “Photodynamic therapy of early esophageal cancer,” Photodiagn. Photodynam. Therapy 5(3), 187–190 (2008).

    Article  Google Scholar 

  64. Yu. Yu. Lur’e, Handbook on Analytical Chemistry (Khimiya, Moscow, 1987) [in Russian].

    Google Scholar 

  65. S. Schmidt and D. V. Volodkin, “Microparticulate biomolecules by mild CaCO3 templating,” J. Mater. Chem. B 1(9), 1210–1218 (2013).

    Article  Google Scholar 

  66. A. S. E. Ojugo, P. M. McSheehy, D. J. McIntyre, C. McCoy, M. Stubbs, M. O. Leach, M. O. Leach, I. R. Judson, and J. R. Griffiths, “Measurement of the extracellular pH of solid tumours in mice by magnetic resonance spectroscopy: a comparison of exogenous 19F and 31P probes,” NMR Biomed. 12(8), 495–504 (1999).

    Article  Google Scholar 

  67. M. Stubbs, P. M. McSheehy, J. R. Griffiths, and C. L. Bashford, “Causes and consequences of tumour acidity and implications for treatment,” Molec. Med. Today 6(1), 15–19 (2000).

    Article  Google Scholar 

  68. E. S. Lee, Z. Gao, and Y. H. Bae, “Recent progress in tumor pH targeting nanotechnology,” J. Control. Release 132(3), 164–170 (2008).

    Article  Google Scholar 

  69. Yu. S. Tarakhovskii, Intellectual Lipid Nanocontainers for Targeted Drug Delivery (LKI, Moscow, 2011) [in Russian].

    Google Scholar 

  70. D. V. Volodkin, R. von Klitzing, and H. Möhwald, “Pure protein microspheres by calcium carbonate templating,” Angew. Chem. (Int. Ed. Eng.) 49(48), 9258–9261 (2010).

    Google Scholar 

  71. V. B. Akopyan and Yu. A. Ershov, Foundations of Ultra-sound Interaction with Biological Objects (Bauman Moscow State Technical Univ., Moscow, 2005) [in Russian].

    Google Scholar 

  72. S. S. Berdonosov, I. V. Znamenskaya, and I. V. Melikhov, “Mechanism of the vaterite-to-calcite phase transition under sonication,” Inorg. Mater. 41(12), 1308–1312 (2005).

    Article  Google Scholar 

  73. V. A. Akulichev, “The way to calculate cavitation strength of real liquids,” Akust. Zh. 11(1), 19–23 (1965).

    Google Scholar 

  74. V. Belova, D. A. Gorin, D. G. Shchukin, and H. H. Möhwald, “Selective ultrasonic cavitation on patterned hydrophobic surfaces,” Angew. Chem. (Int. Ed. Eng.) 49(39), 7129–7133 (2010).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yu. I. Svenskaya.

Additional information

Original Russian Text © Yu.I. Svenskaya, N.A. Navolokin, A.B. Bucharskaya, G.S. Terentyuk, A.O. Kuz’mina, M.M. Burashnikova, G.N. Maslyakova, E.A. Lukyanets, D.A. Gorin, 2014, published in Rossiiskie Nanotekhnologii, 2014, Vol. 9, Nos. 7–8.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Svenskaya, Y.I., Navolokin, N.A., Bucharskaya, A.B. et al. Calcium carbonate microparticles containing a photosensitizer photosens: Preparation, ultrasound stimulated dye release, and in vivo application. Nanotechnol Russia 9, 398–409 (2014). https://doi.org/10.1134/S1995078014040181

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1995078014040181

Keywords

Navigation