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.

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.

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.

Colorectal cancer is among the most prevalent and lethal cancers globally. To address this emergency, countries have developed diffuse screening programs and innovative surgical techniques with a consequent decrease in mortality rates in non-metastatic patients. However, five years after diagnosis, metastatic CRC is still characterized by less than 20% survival. Most patients with metastatic CRC cannot be surgically treated. For them, the only option is treatment with conventional chemotherapies, which cause harmful side effects in normal tissues. In this context, nanomedicine can help traditional medicine overcome its limits. Diatomite nanoparticles (DNPs) are innovative nano-based drug delivery systems derived from the powder of diatom shells. Diatomite is a porous biosilica largely found in many areas of the world and approved by the Food and Drug Administration (FDA) for pharmaceutical and animal feed formulations. Diatomite nanoparticles with a size between 300 and 400 nm were shown to be biocompatible nanocarriers capable of delivering chemotherapeutic agents against specific targets while reducing off-target effects. This review discusses the treatment of colorectal cancer with conventional methods, highlighting the drawbacks of standard medicine and exploring innovative options based on the use of diatomite-based drug delivery systems. Three targeted treatments are considered: anti-angiogenetic drugs, antimetastatic drugs, and immune checkpoint inhibitors.

Nanoscale delivery systems have been investigated for therapy due to their advantages, including the sustained delivery of drugs to cells and reduction of systemic toxicity compared to conventional treatments. However, their application is still hampered by experimental challenges, such as the investigation of the drug release in cells rather than in vitro. Here, we describe a hybrid nanoplatform for monitoring the drug release in living colorectal cancer (CRC) cells by Surface-Enhanced Raman Scattering (SERS). Specifically, the anticancer drug Galunisertib is encapsulated in diatomite nanoparticles (DNPs) decorated by gold nanoparticles (AuNPs) and capped by gelatin. The combination of DNP loading capacities with the Raman enhancement of Galunisertib provided by AuNPs enables bio-imaging and drug delivery without using fluorophores or markers, avoiding fluorescence-quenching issues. Thanks to the Raman enhancement of Galunisertib, the drug release profile is monitored and quantified in living cells by SERS with a femtogram scale resolution. When the gelatin shell is digested by proteases, Galunisertib is released and its SERS spectrum decreases, allowing real-time quantification in CRC cells. The therapeutic efficiency of the Galunisertib delivery platform offers an alternative route for lowering drug dose and toxicity.