Characterization of iron oxide nanoparticles for production of breast adenocarcinoma spheroids

MAYELLE  LIMA; Giovana Dias  Silva; Patrícia; Thais; RENÉ; Daniel

doi:10.15392/2319-0612.2024.2695

Autores

MAYELLE LIMA Instituto de Pesquisas Energéticas e Nucleares, 05508-000, São Paulo, Brazil https://orcid.org/0009-0001-2188-0639 (não autenticado)
Giovana Dias Silva Instituto de Pesquisas Energéticas e Nucleares, 05508-000, São Paulo, Brazil
Patrícia Instituto de Pesquisas Energéticas e Nucleares, 05508-000, São Paulo, Brazil https://orcid.org/0000-0002-1825-0097 (não autenticado)
Thais Instituto de Pesquisas Energéticas e Nucleares, 05508-000, São Paulo, Brazil
RENÉ Instituto de Pesquisas Energéticas e Nucleares, 05508-000, São Paulo, Brazil https://orcid.org/0000-0002-7131-204X (não autenticado)
Daniel Instituto de Pesquisas Energéticas e Nucleares, 05508-000, São Paulo, Brazil https://orcid.org/0000-0002-0007-534X (não autenticado)

DOI:

https://doi.org/10.15392/2319-0612.2024.2695

Palavras-chave:

Cultura Tridimensional, Câncer, Nanoparticulas de Ferro, Citotoxicidade

Resumo

A construção de um modelo in vitro que possa demonstrar com precisão as condições encontradas in vivo exige a produção de uma série de complexidades que muitas vezes transcendem várias áreas do conhecimento. Nesse contexto, o presente estudo utilizou a cultura tridimensional por agregação magnética para construir um modelo que representasse, de maneira minimamente satisfatória, as condições para o estudo de comportamentos celulares presentes no ambiente tumoral relacionados à morte e à duplicação celular. Assim, nanopartículas de óxido de ferro funcionalizadas foram usadas para cultivar esferoides tumorais contendo linhagens celulares de adenocarcinoma mamário (MCF7) e fibroblastos humanos (HF002-J) em sua estrutura. Os esferoides foram divididos em categorias de concentração para cada linhagem celular, e, após um processo de triagem, as concentrações com maior estabilidade foram irradiadas ou receberam doses de um fármaco com conhecida atividade antitumoral para tratamento. Os modelos foram estudados por meio de difração de raios-X (DRX), microscopia eletrônica de transmissão (TEM), ensaios de citotoxicidade e microscopia de fluorescência. Os resultados obtidos mostraram ser uma alternativa viável para análises de viabilidade celular, citotoxicidade e morfologia de esferoides tumorais.

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Referências

[1] MARCOM, P.K. Chapter 10 - Breast Cancer. Genomic and Precision Medicine (Third Edition), pp.181-194, 2017.

[2] HERIOT, A. G. 7 - Personalized Cancer Care. Perioperative Care of the Cancer Patient, pp. 83-90, 2023.

[3] ZANONI, M. et al. Modeling neoplastic disease with spheroids and organoids. Journal of Hematology & Oncology, v. 13, 2020.

[4] KHANNA, S. et al. Chapter 13 - Multicellular tumor spheroids as in vitro models for studying tumor responses to anticancer therapies. Animal Biotechnology (Second Edition), pp. 251-268, 2020.

[5] DUTTA, S. et al. Chapter 7 - Remediation of heavy metals with nanomaterials. Separation Science and Technology, v. 15, pp. 97-138, 2022.

[6] LAMICHHANE, N. et al. Chapter 13 - Superparamagnetic iron oxide nanoparticles (SPIONs) as therapeutic and diagnostic agents. Nanoparticle Therapeutics, pp. 455-497, 2022.

[7] TIWARI, A. K. et al. Chapter 10 - Magnetic nanoparticles: challenges and practical considerations. Multifunctional Nanocarriers, pp. 235-257, 2022.

[8] BRAIM, F. S. et al. Rapid green-assisted synthesis and functionalization of superparamagnetic magnetite nanoparticles using Sumac extract and assessment of their cellular toxicity, uptake, and anti-metastasis property. Ceramics International, v. 49, pp. 7359-7369, 2023.

[9] EKE, G. et al. Cell Aggregate Assembly through Microengineering for Functional Tissue Emergence. Cells, v. 11, 2022.

[10] BONFIM, L. et al. Microwave-mediated synthesis of iron-oxide nanoparticles for use in magnetic levitation cell cultures. Appl. Nanosci., pp. 1707–1717, 2019.

[11] OTTENBRITE, R. M. ; JAVAN, R. Biological Structures. Encyclopedia of Condensed Matte Physics, pp. 99–108, 2005.

[12] MALICH, G. et al. The sensitivity and specificity of the MTS tetrazolium assay for detecting the in vitro cytotoxicity of 20 chemicals using human cell lines. Toxicology, v. 124, pp. 179-192, 1997.

[13] KUETE, V. et al. Chapter 10 - Anticancer Activities of African Medicinal Spices and Vegetables. Medicinal Spices and Vegetables from Africa, pp. 271-297, 2017.

[14] DLUDLA, P. V. et al. Chapter 25 - The impact of dimethyl sulfoxide on oxidative stress and cytotoxicity in various experimental models. Toxicology, pp. 243-261, 2021.

[15] ZHOU, Q. M. et al. Curcumin reduces mitomycin C resistance in breast cancer stem cells by regulating Bcl-2 family-mediated apoptosis. Cancer Cell International, v. 17, 2017.

[16] AL-OTAIBI, W. A. et al. Cytotoxicity and apoptosis enhancement in breast and cervical cancer cells upon coadministration of mitomycin C and essential oils in nanoemulsion formulations. Biomedicine & Pharmacotherapy, v. 106, pp. 946-955, 2018.

[17] PIMIA, F. et al. Mitomycin C induces apoptosis and caspase-8 and -9 processing through a caspase-3 and Fas-independent pathway. Cell Death & Differentiation, v. 9, pp. 905-914, 2002.

[18] FISCHER, L. M. et al. Exploration of two methods for quantitative Mitomycin C measurement in tumor tissue in vitro and in vivo. Biological Procedures Online, v. 15, 2013.

[19] BOEDTKJER, E ; PEDERSEN, S. F. The Acidic Tumor Microenvironment as a Driver of Cancerm. Annual Review of Physiology, v. 82, pp. 103–126, 2020.

[20] FANG, Y. P. et al. Diminishing the side effect of mitomycin C by using pH-sensitive liposomes: in vitro characterization and in vivo pharmacokinetics. Drug Des Devel Ther, v. 15, pp. 159-169, 2018.

[21] DLUDLA, P. V. et al. A dose-dependent effect of dimethyl sulfoxide on lipid content, cell viability and oxidative stress in 3T3-L1 adipocytes. Toxicology Reports, pp. 1014-1020, 2018.

[22] ZHANG, W. et al. Optimization of the formation of embedded multicellular spheroids of MCF-7 cells: How to reliably produce a biomimetic 3D model. Analytical Biochemistry, v. 515, pp. 47-54, 2016.

[23] JAYME, C. C. et al. DNA polymer films used as drug delivery systems to early-stage diagnose and treatment of breast cancer using 3D tumor spheroids as a model. Photodiagnosis and Photodynamic Therapy, v. 37, 2022.

[24] ROJAS-CALDERÓN, E. K. et al. Monte Carlo calculations of the cellular S-values for α-particle-emitting radionuclides incorporated into the nuclei of cancer cells of the MDA-MB231, MCF7 and PC3 lines. Applied Radiation and Isotopes, v. 135, pp. 1-6, 2018.

[25] BIALKOWSKA, K. et al. Spheroids as a type of three-dimensional cell cultures—examples of methods of preparation and the most important application. International Journal of Molecular Sciences, v. 21, pp. 1-17, 2020.

[26] CHAN, C. J. et al. Volume Transitions of Isolated Cell Nuclei Induced by Rapid Temperature Increase. Biophysical Journal, v.112, pp. 1063-1076, 2017.

[27] CANTWELL. H. ; NURSE, P. Unravelling nuclear size control. Current Genetics, v. 65, pp. 1281–1285, 2019.

[28] EFREMOV, A. K. et al. Nucleus size and its effect on nucleosome stability in living cells. Biophysical Journal, v. 121, pp. 1-16, 2022.

[29] JEVTIC, P. et al. Concentration-dependent Effects of Nuclear Lamins on Nuclear Size in Xenopus and Mammalian Cells. The Journal of Biological Chemistry, v. 290, pp. 27557-27571, 2015.

[30] LU, W. et al. Nesprin interchain associations control nuclear size. Cellular and Molecular Life Sciences, v. 69, pp. 3493−3509, 2012.

[31] LEBEAUPIN, T. et al. 9 - The Multiple Effects of Molecular Crowding in the Cell Nucleus: From Molecular Dynamics to the Regulation of Nuclear Architecture. Nuclear Architecture and Dynamics, pp.209-232, 2018.

[32] BAIRAMUKOV, V. Y. et al. AFM imaging of the transcriptionally active chromatin in mammalian cells' nuclei. Biochimica et Biophysica Acta (BBA) - General Subjects, v. 1866, 2022.