Selective photodynamic effects on cervical adenocarcinoma cells provided by F127 Pluronic®-based micelles modulating hypericin delivery

Authors

  • Kayane Harumi Mashiba Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá, Maringá, Paraná, Brazil
  • Lucimara Rofrigues Carobeli Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá, Maringá, Paraná, Brazil https://orcid.org/0000-0003-3066-4708
  • Maria Vítoria Felipe de Souza Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá, Maringá, Paraná, Brazil
  • Lyvia Eloiza de Freitas Meirelles Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá, Maringá, Paraná, Brazil
  • Natália Lourenço Mari Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá, Maringá, Paraná, Brazil
  • Gabriel Batista César Department of Chemistry, Universidade Estadual de Maringá, Maringá, Paraná, Brazil
  • Renato Sonchini Gonçalves Department of Chemistry, Universidade Estadual de Maringá, Maringá, Paraná, Brazil
  • Wilker Caetano Department of Chemistry, Universidade Estadual de Maringá, Maringá, Paraná, Brazil
  • Edilson Damke Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá, Maringá, Paraná, Brazil
  • Vânia Ramos Sela da Silva Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá, Maringá, Paraná, Brazil
  • Gabrielle Marconi Zago Ferreira Damke Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá, Maringá, Paraná, Brazil
  • Marcia Edilaine Lopes Consolaro Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringá, Maringá, Paraná, Brazil https://orcid.org/0000-0001-9102-4865

DOI:

https://doi.org/10.1590/s2175-97902023e22459

Keywords:

Photochemotherapy, Endocervical adenocarcinoma, HeLa cells, Hypericin, Pluronic F127, Drug delivery systems

Abstract

Cervical cancer is a leading cause of death among women. The endocervical adenocarcinoma (ECA) represents an aggressive and metastatic type of cancer with no effective treatment options currently available. We evaluated the antitumoral and anti-migratory effects of hypericin (HYP) encapsulated on Pluronic F127 (F127/HYP) photodynamic therapy (PDT) against a human cell line derived from invasive cervical adenocarcinoma (HeLa) compared to a human epithelial cell line (HaCaT). The phototoxicity and cytotoxicity of F127/HYP were evaluated by the following assays: colorimetric assay, MTT, cellular morphological changes by microscopy and long-term cytotoxicity by clonogenic assay. In addition, we performed fluorescence microscopy to analyze cell uptake and subcellular distribution of F127/HYP, cell death pathway and reactive oxygen species (ROS) production. The PDT mechanism was determined with sodium azide and D-mannitol and cell migration by wound-healing assay. The treatment with F127/HYP promoted a phototoxic result in the HeLa cells in a dose-dependent and selective form. Internalization of F127/HYP was observed mainly in the mitochondria, causing cell death by necrosis and ROS production especially by the type II PDT mechanism. Furthermore, F127/HYP reduced the long-term proliferation and migration capacity of HeLa cells. Overall, our results indicate a potentially application of F127/HYP micelles as a novel approach for PDT with HYP delivery to more specifically treat ECA.

Downloads

Download data is not yet available.

References

Agostinis P, Berg K, Cengel KA, Foster TH, Girotti AW, Gollnick SO, et al. Photodynamic therapy of cancer: An update. CA Cancer J Clin 2011;61(4):250-281.

Batrakova EV, Kabanov AV. Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. J Control Release 2008;130(2):98-106.

Buytaert E, Dewaele M, Agostinis P. Molecular effectors of multiple cell death pathways initiated by photodynamic therapy. Biochim Biophys Acta Rev Cancer 2007;1776(1):86-107.

Chen B, De Witte PA. Photodynamic therapy efficacy and tissue distribution of hypericin in a mouse P388 lymphoma tumor model. Cancer Lett 2000;150(1):111-117.

Cheng J, Li W, Tan G, Wang Z, Li S, Jin Y. Synthesis and in vitro photodynamic therapy of chlorin derivative 13 1-ortho-trifluoromethyl-phenylhydrazone modified pyropheophorbide-a. Biomed Pharmacother 2017;87:263-273.

Chung P-S, Saxton RE, Paiva MB, Rhee C-K, Soudant J, Mathey A, et al. Hypericin uptake in rabbits and nude mice transplanted with human squamous cell carcinomas: study of a new sensitizer for laser phototherapy. Laryngoscope 1994;104(12):1471-1476.

Damke GMZF, Damke E, de Souza Bonfim-Mendonça P, Ratti BA, de Freitas Meirelles LE, da Silva VRS, et al. Selective photodynamic effects on cervical cancer cells provided by P123 Pluronic®-based nanoparticles modulating hypericin delivery. Life Sci 2020;255:117858255.

Falk H, Schoppel G. On the synthesis of hypericin by oxidative trimethylemodin anthrone and emodin anthrone dimerization: Isohypericin. Monatshefte Chemie Chem Mon 1992;123(10):931-938.

Franken NAP, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nat Protoc 2006;1(5):2315-2319.

Fuchs J, Thiele J. The role of oxygen in cutaneous photodynamic therapy. Free Radicals Biol Med 1998;24(5):835-847.

Gonçalves RS, Rabello BR, César GB, Pereira PCS, Ribeiro MAS, Meurer EC, et al. An Efficient Multigram Synthesis of Hypericin Improved by a Low Power LED Based Photoreactor. Org Process Res Dev 2017;21(12):2025-2031.

Gregoriou Y, Gregoriou G, Yilmaz V, Kapnisis K, Prokopi M, Anayiotos A, et al. Resveratrol loaded polymeric micelles for theranostic targeting of breast cancer cells. Nanotheranostics 2021;5(1):113.

Hezaveh S, Samanta S, De Nicola A, Milano G, Roccatano D. Understanding the interaction of block copolymers with DMPC lipid bilayer using coarse-grained molecular dynamics simulations. J Phys Chem B 2012;116(49):14333-14345.

Ho YF, Wu MH, Cheng BH, Chen YW, Shih MC. Lipid-mediated preferential localization of hypericin in lipid membranes. Biochim Biophys Acta Biomembr 2009;1788(6):1287-1295.

Hudson JB, Lopez-Bazzocchi I, Towers GHN. Antiviral activities of hypericin. Antiviral Res 1991;15(2):101-12.

Imran M, Shah MR, Shafi U. Amphiphilic block copolymers-based micelles for drug delivery. Des Dev New Nanocarriers 2018;2018:365-400.

Iqbal B, Ghildiyal A, Sahabjada Singh S, Arshad M, Mahdi AA, et al. Antiproliferative and apoptotic effect of curcumin and TRAIL (TNF Related Apoptosis inducing Ligand) in chronic myeloid leukaemic cells. J Clin Diagn Res 2016;10(4):XC01-5.

Karioti A, Bilia AR. Hypericins as Potential Leads for New Therapeutics. Int J Mol Sci 2010;11(2):562.

Kascakova S, Nadova Z, Mateasik A, Mikes J, Huntosova V, Refregiers M, et al. High level of low-density lipoprotein receptors enhance hypericin uptake by U-87 MG cells in the presence of LDL. Photochem Photobiol 2008;84(1):120-127.

Kessel D, Luo Y, Deng Y, Chang CK. The role of subcellular localization in initiation of apoptosis by photodynamic therapy. Photochem Photobiol . 1997;65(3):422-426.

Kubin A, Loew HG, Burner U, Jessner G, Kolbabek H, Wierrani F. How to make hypericin water-soluble. Pharmazie 2008;63:263-269.

Kumar P, Nagarajan A, Uchil PD. Analysis of Cell Viability by the MTT Assay. Cold Spring Harb Protoc 2018;2018(6).

Kurman R, Carcangiu M, Herrington C, Young R. WHO Classification of Tumours of Female Reproductive Organs 4th ed. Kurman R, Carcangiu M, Herrington C, Young R, editors. Lyon: IARC; 2014.

Liang CC, Park AY, Guan JL. In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc . 2007;2(2):329-333.

Loureiro J, Oliva E. The spectrum of cervical glandular neoplasia and issues in differential diagnosis. Arch Pathol Lab Med 2014;138(4):453-483.

Mikeš J, Kleban J, Sačková V, Horváth V, Jamborová E, Vaculová A, et al. Necrosis predominates in the cell death of human colon adenocarcinoma HT-29 cells treated under variable conditions of photodynamic therapy with hypericin. Photochem Photobiol Sci 2007;6(7):758-766.

Nakajima N, Kawashima N. A basic study on Hypericin-PDT in vitro Photodiag Photodyn Ther 2012;9(3):196-203.

Nam G, Rangasamy S, Ju H, Samson AAS, Song JM. Cell death mechanistic study of photodynamic therapy against breast cancer cells utilizing liposomal delivery of 5,10,15,20-tetrakis(benzo[b]thiophene) porphyrin. J Photochem Photobiol B 2016;166:116-125.

Niedre M, Patterson MS, Wilson BC. Direct near-infrared luminescence detection of singlet oxygen generated by photodynamic therapy in cells in vitro and tissues in vivo. Photochem Photobiol . 2002;75(4):382-391.

Nwahara N, Abrahams G, Prinsloo E, Nyokong T. Folic acid-modified phthalocyanine-nanozyme loaded liposomes for targeted photodynamic therapy. Photodiagnosis Photodyn. Ther 2021;36.

Ochsner M. Photophysical and photobiological processes in the photodynamic therapy of tumours. J Photochem Photobiol B 1997;39(1):1-18.

Paik ES, Lim MC, Kim MH, Kim YH, Song ES, Seong SJ, et al. Prognostic Model for Survival and Recurrence in Patients with Early-Stage Cervical Cancer: A Korean Gynecologic Oncology Group Study (KGOG 1028). Cancer Res Treat 2020;52(1):320-333.

Robertson CA, Evans DH, Abrahamse H. Photodynamic therapy (PDT): A short review on cellular mechanisms and cancer research applications for PDT. J Photochem Photobiol B 2009;96(1):1-8.

de Souza MVF, Shinobu-Mesquita C, Meirelles LE, Mari N, César G, Gonçalves R, et al. Effects of hypericin encapsulated on Pluronic F127 photodynamic therapy against triple negative breast cancer. Asian Pac J Cancer Prev 2022;23(5):1741-1751.

Stolnicu S, Hoang L, Soslow RA. Recent advances in invasive adenocarcinoma of the cervix. Virchows Arch 2019;475(5):537-549.

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin . 2021;71(3):209-249.

Tatischeff I, Alfsen A. A New Biological Strategy for Drug Delivery: Eucaryotic Cell-Derived Nanovesicles. J Biomater Nanobiotechnol 2011;2(5):494-499.

Theodossiou TA, Hothersall JS, De Witte PA, Pantos A, Agostinis P. The multifaceted photocytotoxic profile of hypericin. Mol Pharm 2009;6(6):1775-1789.

Xu L, Zhang X, Cheng W, Wang Y, Yi K, Wang Z, et al. Hypericin-photodynamic therapy inhibits the growth of adult T-cell leukemia cells through induction of apoptosis and suppression of viral transcription. Retrovirol 2019;16(1):1-13.

Yokoi E, Mabuchi S, Takahashi R, Matsumoto Y, Kuroda H, Kozasa K, et al. Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy: adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma. J Gynecol Oncol 2017;28(2):e19.

Zhang X, Jackson JK, Burt HM. Development of amphiphilic diblock copolymers as micellar carriers of taxol. Int J Pharm 1996;132(1-2):195-206.

Downloads

Published

2023-05-22

Issue

Section

Original Article

How to Cite

Selective photodynamic effects on cervical adenocarcinoma cells provided by F127 Pluronic®-based micelles modulating hypericin delivery. (2023). Brazilian Journal of Pharmaceutical Sciences, 59, e22459. https://doi.org/10.1590/s2175-97902023e22459