**5. Conclusions**

Using electrochemical etching, we produced mesoporous silicon substrates functionalized with gold nanoparticles. Due to their porous structures, the substrates behave as a drug delivery system, where drugs or other agents loaded in the matrix are released over time with a first order kinetics and a time constant that can be varied by tuning the characteristics of the pores. Due to its nanostructure, the device can amplify by several orders of magnitude the signal generated by molecules in the cell membrane during the process of adhesion and migration. These nanodevices combine therapy and diagnostics effects in the same device, with the primary advantage of not being limited to therapy or sensing, as they provide coincident diagnostic information plus delivery of therapeutics. For their capabilities to drive cell growth and high capacities of therapeutic loading, these devices can be possibly used in tissue engineering, regenerative medicine, and nanomedicine. In these fields, the

ability to assemble cells together has to be associated with the ability of deliver therapeutics accurately to achieve maximum control over cell fate. The ability of the system to measure adhesion at the nanoscale, is an extra feature that makes this theranostics device the ideal candidate for those who want to design substrates for cell growth and proliferation or, vice versa, induce apoptosis in tumor cells with unprecedented control.

In this work, by varying the parameters of the process we obtained substrates with di fferent values of pore size, porosity, and roughness. MeP1 substrates exhibit smaller values of pore size (PS ≈ 11 nm) and roughness (Ra ≈ 7 nm), but have a larger fractal dimension (Df ≈ 2.48) compared to MeP2 substrates, with PS ≈ 21 nm, Ra ≈ 13 nm, and Df ≈ 2.15. Adhesion of MCF-7 cells was accelerated on MeP1 substrates with larger value of fractal dimension compared to MeP2 substrates and flat silicon used as a control.

When we considered the e ffect of the release over time of an anti-tumor drug, we observed that the maximum reduction of cell growth is found for MeP2 substrates 36 and 48 h after seeding, with a decrease in the number of adhering cells up to 87% with respect to the same substrates without drug. A total of 72 h from cell culture, the therapeutics e fficacy of MeP2 substrates falls to 44%, and is overtaken by MeP1 silicon, with a cell number contraction of 90%, reflecting the di fferent morphological characteristics of surfaces.

Results sugges<sup>t</sup> that the adhesive properties of mesoporous substrates, the kinetics of drug delivery, and the e ffects that a combination of the two may have on the adhesion and proliferation of cells, can be conveniently modulated by changing the pore size and roughness in the narrow intervals of PS ≈ 11–21 nm and Ra ≈ 7–13 nm.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/1999-4923/12/5/481/s1, Supporting Information 1: Determining the porosity of Mesoporous surfaces. Supporting Information 2: Extracting Au nano-particle diameter.

**Author Contributions:** Conceptualization, F.G.; methodology, M.L.C., G.M., M.D.A., S.D.V., A.I. and L.T.; software, V.O.; validation, V.O., M.L.C., G.P., E.D.F., P.C., N.M. and F.G.; formal analysis, M.L.C., V.O., E.D.F., N.M. and F.G.; investigation, M.L.C., N.M. and F.G.; resources, N.M. and F.G.; data curation, M.L.C., V.O., N.M. and F.G.; writing—original draft preparation, F.G.; writing—review and editing, M.L.C., V.O., N.M., F.G.; visualization, M.L.C. and F.G.; supervision, G.P., E.D.F., P.C., N.M., F.G.; project administration, N.M. and F.G.; funding acquisition, N.M. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** We thank the Dresden Center for Nanoanalysis of Technische Universität Dresden for the support provided for the SEM analysis of samples. This publication was supported by the Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro.

**Conflicts of Interest:** The authors declare no conflict of interest.
