Biomaterials Science REVIEW Cite this: DOI: 10.1039/c6bm00872k Received 30th November 2016, Accepted 30th December 2016 DOI: 10.1039/c6bm00872k www.rsc.org/biomaterialsscience Recent applications of the combination of mesoporous silica nanoparticles with nucleic acids: development of bioresponsive devices, carriers and sensors Rafael R. Castillo, Alejandro Baeza and María Vallet-Regí* The discovery and control of the biological roles mediated by nucleic acids have turned them into a powerful tool for the development of advanced biotechnological materials. Such is the importance of these gene-keeping biomacromolecules that even nanomaterials have succumbed to the claimed benefits of DNA and RNA. Currently, there could be found in the literature a practically intractablenumber of examples reporting the use of combination of nanoparticles with nucleic acids, so boundaries are demanded. Following this premise, this review will only cover the most recent and powerful strategies developed to exploit the possibilities of nucleic acids as biotechnological materials when in combination with mesoporous silica nanoparticles. The extensive research done on nucleic acids has significantly incremented the technological possibilities for those biomacromolecules, which could be employed in many different applications, where substrate or sequence recognition or modulation of biological path- ways due to its coding role in living cells are the most promising. In the present review, the chosen counterpart, mesoporous silica nanoparticles, also with unique properties, became a reference material for drug delivery and biomedical applications due to their high biocompatibility and porous structure suit- able for hosting and delivering small molecules. Although most of the reviews dealt with significant advances in the use of nucleic acid and mesoporous silica nanoparticles in biotechnological applications, a rational classification of these new generation hybrid materials is still uncovered. In this review, therewill be covered promising strategies for the development of living cell and biological sensors, DNA-based molecular gates with targeting, transfection or silencing properties, which could provide a significant advance in current nanomedicine. 1. Introduction The development of nanotechnology has significantly increased the number of possibilities for many biological tools. For example, the use of nucleic acids in nanohybrids is destined to become of great importance because it may allow combining, in a single entity, the biotechnological potential of nanoparticles together with the recognition, sensitivity or gene modulation abilities of nucleic acids when applied to living organisms. Moreover, the use of nanoparticles as core platforms for those devices could provide novel and interesting hybrids as detection, diagnosis and/or therapeutic effect features to these devices, 1–3 which are two fundamental applications of nano- particles in biotechnology. Related with cancer, nanometre sized particles offer a unique platform for the development of both therapeutic and diagnosis devices. This effect obeys the particular physiology of solid tumours, which produce inter- actions with nanoparticles and macromolecules in a very par- ticular way, leading to the spontaneous and preferential accumulation, within the tissue, of those particles. This occurs because of the uncontrolled, high and anarchic vascularization of tumours, which produces fenestrations and irregularities that generate aberrant morphologies, which facilitates the accumulation of these within the tumour. Moreover, the associated fast growth results in poor lymphatic drainage, which impedes correct elimination and clearance from the tissue. This combined phenomenon, known as the Enhanced Permeation and Retention (EPR) effect, 4–6 is responsible for turning nanoparticles into Trojan horses able to accumulate and attack solid tumours. Of all the nanoparticles reported to date, Mesoporous Silica Nanoparticles (MSNs) are of great interest because they show Dpto. Química Inorgánica y Bioinorgánica. Facultad de Farmacia, Universidad Complutense de Madrid. Plaza Ramon y Cajal s/n. Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain. E-mail: vallet@ucm.es This journal is © The Royal Society of Chemistry 2017 Biomater. Sci. Published on 20 January 2017. Downloaded by University of Newcastle on 20/01/2017 11:36:52. View Article Online View Journal