The Role of Crocetin-Loaded PLGA Nanoparticles as a Pre-Treatment Agent on Indocyanine-Photodynamic Therapy of Breast Cancer Cell

Document Type : Original Paper

Authors

1 Medical Physics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences ,Mashhad, Iran

Abstract

Introduction: Photodynamic therapy (PDT) can be considered as a non-invasive method for cancer treatment. One of the most commonly of a water-soluble dye photosensitizer (PS) used in photothermal therapy (PTT) and PDT is Indocyanine Green (ICG). However, high cytotoxicity in high concentration and instability in aqueous media were limited its application. It was shown that using nanoparticles or plant extracts in combination with PS could improve PDT efficiency. In this study, anti-cancer properties of crocetin (Crt) loaded PLGA (Poly lactic-co-glycolic acid) nanoparticles (NPs) were utilized to increase the PDT efficacy with ICG on the MCF-7 cells.
Material and Methods: Crt was encapsulated into PLGA NPs and its particle size distribution and encapsulation efficiency were evaluated. IC10 of Crt, PLGA-Crt NPs and ICG was determined by MTT assay in MCF-7 cancer cells. At these concentrations, the cells were pre-treated with Crt or PLG-Crt, then treated with ICG and finally exposure to near infrared (NIR) laser with 2.5 W powers at different times. The cells viability was evaluated by the MTT assay.
Results: The findings showed no dark cytotoxicity due to ICG (12.9 μM), Crt or PLGA-Crt alone. But NIR laser irradiation in the presence of ICG after cells pre-treatment by the Crt or PLGA-Crt NPs leads to induce cell death to (61.6 ±7) % and (75.5 ±5) %, respectively (P<0.05).
Conclusion: The results demonstrated that PLGA-Crt NPs in combination with ICG could improve PDT outcomes more efficiently in comparison with Crt and ICG. Therefore, this method could be effective in breast cancer therapy with low cytotoxicity.

Keywords

Main Subjects


  1. Longo JPF, Muehlmann LA, Miranda-Vilela AL, Portilho FA, de Souza LR, Silva JR, et al. Prevention of Distant Lung Metastasis after Photodynamic Therapy Application in a Breast Cancer Tumor Model. J Biomed Nanotechnol. 2016;12(4):689-99. https://doi.org/10.1166/jbn.2016.2208
  2. Brown SB, Brown EA, Walker I. The present and future role of photodynamic therapy in cancer treatment. Lancet Oncol. 2004;5(8):497-508. https://doi.org/10.1016/S1470-2045(04)01529-3
  3. Villacorta RB, Roque KFJ, Tapang GA, Jacinto SD. Plant extracts as natural photosensitizers in photodynamic therapy: in vitro activity against human mammary adenocarcinoma MCF-7 cells. Asian Pac J Trop Biomed. 2017;7(4):358-66. https://doi.org/10.1016/j.apjtb.2017.01.025
  4. Li B, Chu X, Gao M, Li W. Apoptotic mechanism of MCF-7 breast cells in vivo and in vitro induced by photodynamic therapy with C-phycocyanin. Acta Biochim Biophys Sin. 2010;42(1):80-9. https://doi.org/10.1093/abbs/gmp104
  5. Li L, Huh KM. Polymeric nanocarrier systems for photodynamic therapy. Biomater Res. 2014;18(1):19. https://doi.org/10.1186/2055-7124-18-19
  6. Xiong W, Wang X, Hu J, Liu Y, Liu Q, Wang P. Comparative study of two kinds of repeated photodynamic therapy strategies in breast cancer by using a sensitizer, sinoporphyrin sodium. J Photochem Photobiol B. 2016;160:299-305. https://doi.org/10.1016/j.jphotobiol.2016.04.024
  7. Khdair A, Chen D, Patil Y, Ma L, Dou QP, Shekhar MP, et al. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance. J Control Release. 2010;141(2):137-44. https://doi.org/10.1016/j.jconrel.2009.09.004
  8. Sazgarnia A, Montazerabadi AR, Bahreyni-Toosi MH, Ahmadi A, Aledavood A. In vitro survival of MCF-7 breast cancer cells following combined treatment with ionizing radiation and mitoxantrone-mediated photodynamic therapy. Photodiagnosis Photodyn Ther. 2013;10(1):72-8. https://doi.org/10.1016/j.pdpdt.2012.06.001
  9. ZielińskaB A. Expression of Proapoptotic BAX and TP53 Genes and Antiapoptotic BCL-2 Gene in MCF-7 and T-47D Tumour Cell Cultures of the Mammary Gland After a Photodynamic Therapy with Photolon. Adv Clin Exp Med. 2015:37. https://doi.org/10.17219/acem/38152
  10. Fan W, Huang P, Chen X. Overcoming the Achilles' heel of photodynamic therapy. Chem Soc Rev. 2016,45, 6488-6519. https://doi.org/10.1039/C6CS00616G
  11. Ahn J-C, Kang J-W, Shin J-I, Chung P-S. Combination treatment with photodynamic therapy and curcumin induces mitochondria-dependent apoptosis in AMC-HN3 cells. Int J Oncol. 2012;41(6):2184-90. https://doi.org/10.3892/ijo.2012.1661
  12. Sivasubramanian M, Chuang YC, Lo LW. Evolution of nanoparticle-mediated photodynamic therapy: From superficial to deep-seated cancers. Molecules. 2019 Jan;24(3):520. https://doi.org/10.3390/molecules24030520
  13. Boix-Garriga E, Acedo P, Casadó A, Villanueva A, Stockert JC, Cañete M, et al. Poly (D, L-lactide-co-glycolide) nanoparticles as delivery agents for photodynamic therapy: enhancing singlet oxygen release and photototoxicity by surface PEG coating. Nanotechnology. 2015;26(36):365104. https://doi.org/10.1088/0957-4484/26/36/365104
  14. El-Daly SM, Gamal-Eldeen AM, Abo-Zeid MA, Borai IH, Wafay HA, Abdel-Ghaffar A-RB. Photodynamic therapeutic activity of indocyanine green entrapped in polymeric nanoparticles. Photodiagnosis Photodyn Ther. 2013;10(2):173-85. https://doi.org/10.1016/j.pdpdt.2012.08.003
  15. Akbari T, Pourhajibagher M, Chiniforush N, Shahabi S, Hosseini F, Bahador A. Improve ICG based photodynamic properties through conjugation of icg into nano-graphene oxide against enterococcus faecalis. Avicenna J Clin Microbiol Infect. 2018;5(1): e64624. https://doi.org/10.5812/ajcmi.64624
  16. Zheng X, Zhou F, Wu B, Chen WR, Xing D. Enhanced tumor treatment using biofunctional indocyanine green-containing nanostructure by intratumoral or intravenous injection. Mol Pharm. 2012;9(3):514-22. https://doi.org/10.1021/mp200526m
  17. Montazerabadi AR, Sazgarnia A, Bahreyni-Toosi MH, Ahmadi A, Aledavood A. The effects of combined treatment with ionizing radiation and indocyanine green-mediated photodynamic therapy on breast cancer cells. J Photochem Photobiol B. 2012;109:42-9. https://doi.org/10.1016/j.jphotobiol.2012.01.004
  18. Ghorbani F, Attaran-Kakhki N, Sazgarnia A. The synergistic effect of photodynamic therapy and photothermal therapy in the presence of gold-gold sulfide nanoshells conjugated Indocyanine green on HeLa cells. Photodiagnosis Photodyn Ther. 2017;17:48-55. https://doi.org/10.1016/j.pdpdt.2016.10.002
  19. Skřivanová K, Škorpíková J, Švihálek J, Mornstein V, Janisch R. Photochemical properties of a potential photosensitiser indocyanine green in vitro. J Photochem Photobiol B. 2006;85(2):150-4. https://doi.org/10.1016/j.jphotobiol.2006.06.004
  20. Kim SH, Lee JM, Kim SC, Park CB, Lee PC. Proposed cytotoxic mechanisms of the saffron carotenoids crocin and crocetin on cancer cell lines. Biochem Cell Biol. 2014;92(2):105-11. https://doi.org/10.1139/bcb-2013-0091
  21. G Gutheil W, Reed G, Ray A, Anant S, Dhar A. Crocetin: an agent derived from saffron for prevention and therapy for cancer. Curr Pharm Biotechnol. 2012;13(1):173-9. https://doi.org/10.2174/138920112798868566
  22. Zhong Y-j, Shi F, Zheng X-l, Wang Q, Yang L, Sun H, et al. Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53-dependent and-independent mechanisms. Acta Pharmacol Sin. 2011;32(12):1529-36. https://doi.org/10.1038/aps.2011.109
  23. He K, Si P, Wang H, Tahir U, Chen K, Xiao J, et al. Crocetin induces apoptosis of BGC-823 human gastric cancer cells. Mol Med Rep. 2014;9(2):521-6. https://doi.org/10.3892/mmr.2013.1851
  24. Pradhan J, Mohanty C, Sahoo SK. Protective efficacy of crocetin and its nanoformulation against cyclosporine A-mediated toxicity in human embryonic kidney cells. Life Sci. 2019;216:39-48. https://doi.org/10.1016/j.lfs.2018.11.027
  25. Hafezi Ghahestani Z, Alebooye Langroodi F, Mokhtarzadeh A, Ramezani M, Hashemi M. Evaluation of anti-cancer activity of PLGA nanoparticles containing crocetin. Artif Cells Nanomed Biotechnol. 2016:1-6. https://doi.org/10.1080/21691401.2016.1198359
  26. Langroodi F, Hafezi Ghahestani Z, Alibolandi M, Ebrahimian M, Hashemi M. Evaluation of the effect of crocetin on antitumor activity of doxorubicin encapsulated in PLGA nanoparticles. Nanomed J. 2016;3(1):23-34. https://doi.org/10.22038/NMJ.2016.6193
  27. Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V. PLGA-based nanoparticles: an overview of biomedical applications. J Control Release. 2012;161(2):505-22. https://doi.org/10.1016/j.jconrel.2012.01.043
  28. Swed A, Cordonnier T, Fleury F, Boury F. Protein Encapsulation into PLGA Nanoparticles by a Novel Phase Separation Method Using Non-Toxic Solvents. J Nanomed Nanotechnol. 2014;5(241):2. https://doi.org/10.4172/2157-7439.1000241
  29. Paszko E, Ehrhardt C, Senge MO, Kelleher DP, Reynolds JV. Nanodrug applications in photodynamic therapy. Photodiagnosis Photodyn Ther. 2011;8(1):14-29. https://doi.org/10.1016/j.pdpdt.2010.12.001
  30. Plackal Adimuriyil George B, Abrahamse H. A review on novel breast cancer therapies: Photodynamic therapy and plant derived agent induced cell death mechanisms. Anticancer Agents Med Chem. 2016;16(7):793-801. https://doi.org/10.2174/1871520615666151026094028
  31. Marrelli M, Menichini G, Provenzano E, Conforti F. Applications of natural compounds in the photodynamic therapy of skin cancer. Curr Med Chem. 2014;21(12):1371-90. https://doi.org/10.2174/092986732112140319094324
  32. Gift MM, Ann KC, Ivan M-T, Heidi A. A review of nanoparticle photosensitizer drug delivery uptake systems for photodynamic treatment of lung cancer. Photodiagnosis Photodyn Ther. 2018;1(22):147-54. https://doi.org/10.1016/j.pdpdt.2018.03.006
  33. Saxena V, Sadoqi M, Shao J. Polymeric nanoparticulate delivery system for Indocyanine green: biodistribution in healthy mice. Int J Pharm. 2006;308(1):200-4. https://doi.org/10.1016/j.ijpharm.2005.11.003