ZnO Tetrapods for Label-Free Optical Biosensing: Physicochemical Characterization and Functionalization Strategies.

In this study, we fabricated three different ZnO tetrapodal nanostructures (ZnO-Ts) by a combustion process and studied their physicochemical properties by different techniques to evaluate their potentiality for label-free biosensing purposes. Then, we explored the chemical reactivity of ZnO-Ts by quantifying the available functional hydroxyl groups (-OH) on the transducer surface necessary for biosensor development. The best ZnO-T sample was chemically modified and bioconjugated with biotin as a model bioprobe by a multi-step procedure based on silanization and carbodiimide chemistry. The results demonstrated that the ZnO-Ts could be easily and efficiently biomodified, and sensing experiments based on the streptavidin target detection confirmed these structures' suitability for biosensing applications.

ROS-Generating Hyaluronic Acid-Modified Zirconium Dioxide-Acetylacetonate Nanoparticles as a Theranostic Platform for the Treatment of Osteosarcoma.

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.

Design of Gelatin-Capped Plasmonic-Diatomite Nanoparticles with Enhanced Galunisertib Loading Capacity for Drug Delivery Applications.

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.

SERS Quantification of Galunisertib Delivery in Colorectal Cancer Cells by Plasmonic-Assisted Diatomite Nanoparticles.

The small molecule Galunisertib (LY2157299, LY) shows multiple anticancer activities blocking the transforming growth factor-ß1 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.

Bioconjugation of a PNA Probe to Zinc Oxide Nanowires for Label-Free Sensing.

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.