Álvaro Artiga1 2 Sonia García-Embid1 2 Inés Serrano-Sevilla1 2 Gabriel Alfranca1 Laura De Matteis3 2 Scott G. Mitchell1 2 Carlos Sánchez-Somolinos1 2 Jesús M. de la Fuente1 2

1, Instituto de Ciencia de Materiales de Aragon (ICMA), CSIC/University of Zaragoza, Zaragoza, , Spain
2, CIBER-BBN, Instituto de Salud Carlos III, Madrid, , Spain
3, Instituto de Nanociencia de Aragon (INA), University of Zaragoza, Zaragoza, , Spain

The unique physicochemical properties of gold nanoparticles (AuNPs) make them highly applicable for drug release, optoacoustic imaging, biosensing and photothermal therapy, among others. This work highlights unique methodologies for the encapsulation of AuNPs in chitosan hydrogels to increase their applicability and efficacy in health-related applications, in particular for photothermal therapy (PTT).
In PTT, AuNPs are employed to convert light energy into heat for the selective ablation of target cells. Anisotropic AuNPs such as nanoprisms, rods and stars, are frequently employed because they absorb near-infrared light that is harmless for surrounding cells. In previous work, we have compared the heating capability, cellular internalization, toxicity and thermoablation capacity of two different types of anisotropic AuNPs: gold nanorods (AuNRs) and nanoprisms (AuNPrs) [1]. Although both AuNPs were highly efficient photothermal converters, AuNRs possessed a more efficient heating capability. However, the in vitro thermoablation studies clearly demonstrated that AuNPrs were more effective at inducing cell death by PTT due to their greater cellular internalization, while AuNRs could not be employed for this purpose due to their extremely low cellular internalization.
We succeeded in improving the PTT application of AuNRs by entrapping them inside a cell-adhesive chitosan hydrogel using anionic polyoxometalates (POMs) as gelling agents [2]. These functional nanocontainers remained non-cytotoxic and presented the ability to adhere to the cytoplasmic membranes of cells avoiding any need for cellular internalization, thus rendering them as highly efficient PTT agents. However, one key disadvantage of this entrapment methodology is the lack of control of the size and size-dispersion of the nanocontainers.
In order to improve these drawbacks, we have developed a novel strategy for AuNP microencapsulation in chitosan hydrogel by inkjet printing [3]. Inkjet printing, as a high-throughput, continuous and automatic technology poses relevant industrial potential for microencapsulation. In particular, our approach has showed a high rate of production, excellent control of the microcapsules size, high encapsulation efficiency and ease of scale-up; obtaining almost monodisperse chitosan microcapsules containing AuNPs. We are currently studying the use of these chitosan hydrogels for oral administration of gold nanoparticles in vitro and in vivo.

[1] Artiga, Á., Alfranca, G., Stepien, G., Moros, M., Mitchell, S. G., and de la Fuente, J. M. (2016). Nanomedicine 11, 2903–2916. doi: 10.2217/nnm-2016-0257
[2] Artiga, Á., García-Embid, S., Matteis, L. D., Mitchell, S. G., and de la Fuente, J. M. (2018). Front. Chem. doi: 10.3389/fchem.2018.00234
[3] Artiga, Á., Serrano-Sevilla, I., Matteis, L. D., Mitchell, S. G., Sánchez-Somolinos, C., and de la Fuente, J. M. (2018). (In preparation)