*Article* **Cell Theranostics on Mesoporous Silicon Substrates**

**Maria Laura Coluccio 1,**†**, Valentina Onesto 1,**†**, Giovanni Marinaro 2,3, Mauro Dell'Apa 4, Stefania De Vitis 1, Alessandra Imbrogno 5, Luca Tirinato 1, Gerardo Perozziello 1, Enzo Di Fabrizio 6, Patrizio Candeloro 1, Natalia Malara 1,\*,**‡ **and Francesco Gentile 4,\*,**‡


Received: 27 April 2020; Accepted: 21 May 2020; Published: 25 May 2020

**Abstract:** The adhesion, proliferation, and migration of cells over nanomaterials is regulated by a cascade of biochemical signals that originate at the interface of a cell with a substrate and propagate through the cytoplasm to the nucleus. The topography of the substrate plays a major role in this process. Cell adhesion molecules (CAMs) have a characteristic size of some nanometers and a range of action of some tens of nanometers. Controlling details of a surface at the nanoscale—the same dimensional over which CAMs operate—offers ways to govern the behavior of cells and create organoids or tissues with heretofore unattainable precision. Here, using electrochemical procedures, we generated mesoporous silicon surfaces with different values of pore size (PS ≈ 11 nm and PS ≈ 21 nm), roughness (Ra ≈ 7 nm and Ra ≈ 13 nm), and fractal dimension (Df ≈ 2.48 and Df ≈ 2.15). Using electroless deposition, we deposited over these substrates thin layers of gold nanoparticles. Resulting devices feature (i) nanoscale details for the stimulation and control of cell assembly, (ii) arrays of pores for drug loading/release, (iii) layers of nanostructured gold for the enhancement of the electromagnetic signal in Raman spectroscopy (SERS). We then used these devices as cell culturing substrates. Upon loading with the anti-tumor drug PtCl (O,O-acac)(DMSO) we examined the rate of adhesion and growth of breast cancer MCF-7 cells under the coincidental effects of surface geometry and drug release. Using confocal imaging and SERS spectroscopy we determined the relative importance of nano-topography and delivery of therapeutics on cell growth—and how an unbalance between these competing agents can accelerate the development of tumor cells.

**Keywords:** nanoporous silicon; gold nanoparticles; drug delivery; cancer cells; theranostics
