(176k) Closer to Reality: Development of Biocompatible Hydrogels to Validate Antitumor Activity and Specificity of a New Targeted paclitaxel Nanovehicle through 3D Cell Cultures

Currently, the first step for the validation of novel antitumor therapies is usually based on testing on two-dimensional cell cultures. Nevertheless, the drawbacks of such conventional cultures are already well-known and have been identified in the literature. One of the most important disadvantages of 2D cultures as testing platforms is the fact that cells are super-nourished and super-oxygenated and. Moreover, they are forced to polarize and often immortalized. As a consequence, even the most successful 2D studies do not correlate to in vivo results and further research has become essential [1].

Thus, numerous research groups are now focusing on the development of 3D cancer cell cultures or tumor spheroids, grown in specialized gels or matrices, which better mimic natural tumor conditions [2]. Thereby, this is the main goal of the present work: fabricating a hydrogel using biocompatible materials such as silk fibroin and gellan gum, which allows to 3D-culture cells from the HER2-positive breast carcinoma cell line BT474 to validate the therapeutic action and specificity of a novel paclitaxel-trastuzumab combined nanovehicle synthetized in a previous work.

To achieve this objective, BT474 cells were cultured and introduced to form tumor spheroids, and their growth into the hydrogel was characterized. Consequently, they were treated with the aforementioned paclitaxel-trastuzumab combined nanovehicle. Obtained results have been compared to the already verified nanovehicle’s antitumor effect in conventional 2D cultures and, in this manner, the establishment of a more accurate in vitro validation method has been achieved.

References

[1] Alemany-Ribes M., Semino C.E. Adv. Drug Deliv. Rev., 2014, 79-80, 40-49.

[2] Gurski L.A., Jha A.K., Zhang C., Jia X, Farach-Carson M.C. Biomaterials, 2009, 30, 6076-6085.

[3] Román J.V., Rodríguez-Rodríguez J.A., Martín del Valle E.M., Galán M.A. Polym. Adv. Technol., 2016, 27, 623-629.