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.

Current advances in the fabrication of smart nanomaterials and nanostructured surfaces find wide usage in the biomedical field. In this context, nanosensors based on localized surface plasmon resonance exhibit unprecedented optical features that can be exploited to reduce the costs, analytic times, and need for expensive lab equipment. Moreover, they are promising for the design of nanoplatforms with multiple functionalities (e.g., multiplexed detection) with large integration within microelectronics and microfluidics. In this review, we summarize the most recent design strategies, fabrication approaches, and bio-applications of plasmonic nanoparticles (NPs) arranged in colloids, nanoarrays, and nanocomposites. After a brief introduction on the physical principles behind plasmonic nanostructures both as inherent optical detection and as nanoantennas for external signal amplification, we classify the proposed examples in colloid-based devices when plasmonic NPs operate in solution, nanoarrays when they are assembled or fabricated on rigid substrates, and nanocomposites when they are assembled within flexible/polymeric substrates. We highlight the main biomedical applications of the proposed devices and offer a general overview of the main strengths and limitations of the currently available plasmonic nanodevices.

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.

Zinc oxide nanowires (ZnONWs) are largely used in biosensing applications due to their large specific surface area, photoluminescence emission and electron mobility. In this work, the surfaces of ZnONWs are modified by covalent bioconjugation of a peptidic nucleic acid (PNA) probe whose sequence is properly chosen to recognize a complementary DNA (cDNA) strand corresponding to a tract of the CD5 mRNA, the main prognostic marker of chronic lymphatic leukemia. The interaction between PNA and cDNA is preliminarily investigated in solution by circular dichroism, CD melting, and polyacrylamide gel electrophoresis. After the immobilization of the PNA probe on the ZnONW surface, we demonstrate the ability of the PNA-functionalized ZnONW platform to detect cDNA in the μM range of concentration by electrical, label-free measurements. The specificity of the sensor is also verified against a non-complementary DNA sequence. These preliminary results highlight the potential application of PNA-bioconjugated ZnONWs to label-free biosensing of tumor markers.

Materials that are able to produce free radicals have gained increasing attention for environmental and biomedical purposes. Free radicals, such as the superoxide anion (O₂^•−), act as secondary messengers in many physiological pathways, such as cell survival. Therefore, the production of free radicals over physiological levels has been exploited in the treatment of different types of cancer, including osteosarcoma (OS). In most cases, the production of reactive oxygen species (ROS) by materials is light-induced and requires the use of chemical photosensitisers, making it difficult and expensive. Here, for the first time, we propose photoluminescent hybrid ZrO₂-acetylacetonate nanoparticles (ZrO₂-acac NPs) that are capable of generating O₂^•− without light activation as an adjuvant for the treatment of OS. To increase the uptake and ROS generation in cancer cells, we modify the surface of ZrO₂-acac NPs with hyaluronic acid (HA), which recognizes and binds to the surface antigen CD44 overexpressed on OS cells. Since these nanoparticles emit in the visible range, their uptake into cancer cells can be followed by a label-free approach. Overall, we show that the generation of O₂^•− is toxic to OS cells and can be used as an adjuvant treatment to increase the efficacy of conventional drugs.