Diatoms—unicellular photosynthetic algae—are promising natural sources of nanostructured silica. These microorganisms produce in their membrane approximately a highly ordered porous cell wall called a frustule as protection from environmental stress. Diatom frustules consist of hydrated silica that show peculiar properties including biocompatibility, tailorable surface chemistry, chemical inertness, and thermal stability. Frustules harvested from aquatic ecosystems or diatomaceous fossil sediments represent an excellent cost-effective source of biosilica for a broad range of biomedical applications. The porous ultrastructure of the frustules displays a large surface area available for coating with various biomolecules through different functionalization methods. In this review article, we highlight the main features of diatom biosilica and present some of the most advantageous properties that support the employment of frustules in the field of drug delivery, biosensing, and regenerative medicine. In particular, it is offered an insight into the most common functionalization strategies through which diatom physicochemical properties can be modified and tailored according to the described field of application.

therapies for CRC treatment, like systemic chemotherapy and immunotherapy, are expensive and invasive since they fail to target cancer cells selectively, causing severe toxicity on normal tissues besides side effects. [2][3][4][5] The epithelial-to-mesenchymal transition (EMT) is a dynamic multistep process involved in several physiological and pathological conditions, including cancer. [6] Notably, EMT in CRC is associated with an invasive, metastatic, and chemoresistant phenotype. [7] In contrast, the mesenchymal-to-epithelial transition (MET), is the reverse program of EMT in metastases and is characterized by the upregulation of epithelial adhesive proteins such as E-CADHERIN, and downregulation of mesenchymal proteins, such as SNAIL-1 and TWIST-1. Slowing EMT or even reversing the process in metastases inducing a MET program not only is a powerful therapeutic approach alone, but can also assist in increasing the efficacy of other anticancer treatments. Among the molecular pathways promoting tumorigenesis in CRC, the transforming growth factor-β (TGF-β) is described as a crucial factor in EMT induction. [8] Fighting the CRC with the TGF-β receptor I-specific inhibitor Galunisertib (LY2157299, LY) has been proposed as a powerful strategy to reduce tumor growth and the risk of relapse. [8] However, LY is cleared predominantly by cytochrome P450 3A4 (CYP3A4) oxidative metabolism in the The small molecule Galunisertib (LY2157299, LY) shows multiple anticancer activities blocking the transforming growth factor-β1 receptor, responsible for the epithelial-to-mesenchymal transition (EMT) by which colorectal cancer (CRC) cells acquire migratory and metastatic capacities. However, frequent dosing of LY can produce highly toxic metabolites. Alternative strategies to reduce drug side effects can rely on nanoscale drug delivery systems that have led to a medical revolution in the treatment of cancer, improving drug efficacy and lowering drug toxicity. Here, a hybrid nanosystem (DNP-AuNPs-LY@Gel) made of a porous diatomite nanoparticle decorated with plasmonic gold nanoparticles, in which LY is retained by a gelatin shell, is proposed. The multifunctional capability of the nanosystem is demonstrated by investigating the efficient LY delivery, the enhanced EMT reversion in CRCs and the intracellular quantification of drug release with a sub-femtogram resolution by surface-enhanced Raman spectroscopy (SERS). The LY release trigger is the pH sensitivity of the gelatin shell to the CRC acidic microenvironment. The drug release is real-time monitored at single-cell level by analyzing the SERS signals of LY in CRC cells. The higher efficiency of LY delivered by the DNP-AuNPs-LY@Gel complex paves the way to an alternative strategy for lowering drug dosing and consequent side effects.

Inorganic diatomite nanoparticles (DNPs) have gained increasing interest as drug delivery systems due to their porous structure, long half-life, thermal and chemical stability. Gold nanoparticles (AuNPs) provide DNPs with intriguing optical features that can be engineered and optimized for sensing and drug delivery applications. In this work, we combine DNPs with gelatin stabilized AuNPs for the development of an optical platform for Galunisertib delivery. To improve the DNP loading capacity, the hybrid platform is capped with gelatin shells of increasing thicknesses. Here, for the first time, full optical modeling of the hybrid system is proposed to monitor both the gelatin generation, degradation, and consequent Galunisertib release by simple spectroscopic measurements. Indeed, the shell thickness is optically estimated as a function of the polymer concentration by exploiting the localized surface plasmon resonance shifts of AuNPs. We simultaneously prove the enhancement of the drug loading capacity of DNPs and that the theoretical modeling represents an efficient predictive tool to design polymer-coated nanocarriers.