Modelos de co-culturas contendo células cancerígenas para testar novos sistemas terapêuticos

Na atualidade, a nanotecnologia é considerada uma ferramenta fundamental para o desenvolvimento de novos sistemas de entrega de fármacos, como por exemplo as nanopartículas. Contudo, antes de estes veículos poderem ser usados na luta contra o cancro, estes devem ser testados em condições que reproduzam as condições nativas encontradas nos tumores que afectam os seres humanos. In vivo, os tumores são massas complexas de tecido constituído por células cancerígenas rodeados por células do estroma, principalmente fibroblastos. Estas células do estroma desempenham um papel fundamental na regulação do comportamento das células cancerígenas, pois podem contribuir para aumentar a resistência que as células cancerígenas apresentam às drogas. Assim, os modelos de co-culturas, com células cancerígenas e fibroblastos, têm sido bastante usados no desenvolvimento de nanopartículas para fins terapêuticos. No presente estudo foram usados diferentes rácios de células do cancro da mama e fibroblastos, de forma a representar melhor a heterogeneidade do cancro da mama. Os resultados obtidos por microscopia confocal e citometria de fluxo demonstraram que diferentes concentrações de fibroblastos nas co-culturas podem influenciar a capacidade de internalização celular das nanopartículas poliméricas em estudo.

Abstract:

Co-culture models are currently bridging the gap between classical cultures and in vivo animal models. Exploring this novel approach unlocks the possibility to mimic the tumor microenvironment in vitro, through the establishment of cancer-stroma synergistic interactions. Notably, these organotypic models offer a perfect platform for the development and pre-clinical evaluation of candidate nanocarriers loaded with anti-tumoral drugs in a high throughput screening mode, with lower costs and absence of ethical issues. However, this evaluation was until now limited to co-culture systems established with precise cell ratios, not addressing the natural cell heterogeneity commonly found in different tumors. Therefore, herein the multifunctional nanocarriers efficiency was characterized in various fibroblast-MCF-7 co-culture systems containing different cell ratios, in order to unravel key design parameters that influence nanocarrier performance and the therapeutic outcome. The successful establishment of the co-culture models was confirmed by the tissue-like distribution of the different cells in culture. Nanoparticles incubation in the various co-culture systems reveals that these nanocarriers possess targeting specificity for cancer cells, indicating their suitability for being used in this illness therapy. Additionally, by using different co-culture ratios, different nanoparticle uptake profiles were obtained. These findings are of crucial importance for the future design and optimization of new drug delivery systems, since their real targeting capacity must be addressed in heterogeneous cell populations, such as those found in tumors.

Journal:

PLoS ONE

Link:

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0070072

DOI:

http://dx.doi.org/10.1371/journal.pone.0070072