Luisa De Cola

Increasing larval settlement can substantially accelerate coral reef restoration by overcoming a key bottleneck in coral population recovery. Successful settlement depends on biological and chemical cues associated with microbial biofilms and crustose coralline algae that are often reduced or absent on degraded reefs. Here, we present two complementary nanocarrier strategies for delivering a single defined bacterial settlement signal, lipopolysaccharides (LPS), from hydrogel coatings applied to coral settlement surfaces. One platform presents LPS at the hydrogel surface using liposome nanoparticles, while the other encapsulates LPS in silica nanoparticles embedded in the hydrogel matrix for gradual release. Both systems increased settlement of Montipora capitata larvae by >5-fold compared to uncoated control surfaces. Because this approach relies on a single cue derived from cultured bacteria, it offers a potentially scalable alternative to live biofilms or complex natural extracts. These results establish a promising biomaterials strategy for enhancing coral recruitment and supporting reef restoration.

Self‐assembly is a well‐known phenomenon in nature, occurring at all scales, from small molecules to complex biomolecules, and it is the foundation for the formation of hierarchical biological structures. Pivotal is the requirement for precise organization through supramolecular interactions, which often trigger dramatic changes in reactivity, spectroscopic features and functional outcomes. Here, we demonstrate that the self‐assembly of a Pt(II) complex not only gives rise to a superior imaging probe, but also to the emergence of redox‐active features. Once in vivo, the self‐assembled Pt(II) complex surprisingly acts as a potent promoter of stem cell proliferation and a modulator of key physiological functions. The assembled luminescent complexes finely tune reactive oxygen species (ROS) response in the transparent freshwater polyp Hydra vulgaris , enhancing the total antioxidant capacity and modulating the expression of key genes involved in antioxidant defenses and cell cycle progression. In addition, in the sea anemone Nematostella vectensis , the assembled complex accelerates the larvae‐to‐adult metamorphosis process, further underscoring its multifaceted role and species‐specific action in diverse biological systems and ultimately paving the way for innovative theranostic strategies.

Self‐assembly is a well‐known phenomenon in nature, occurring at all scales, from small molecules to complex biomolecules, and it is the foundation for the formation of hierarchical biological structures. Pivotal is the requirement for precise organization through supramolecular interactions, which often trigger dramatic changes in reactivity, spectroscopic features and functional outcomes. Here, we demonstrate that the self‐assembly of a Pt(II) complex not only gives rise to a superior imaging probe, but also to the emergence of redox‐active features. Once in vivo, the self‐assembled Pt(II) complex surprisingly acts as a potent promoter of stem cell proliferation and a modulator of key physiological functions. The assembled luminescent complexes finely tune reactive oxygen species (ROS) response in the transparent freshwater polyp Hydra vulgaris , enhancing the total antioxidant capacity and modulating the expression of key genes involved in antioxidant defenses and cell cycle progression. In addition, in the sea anemone Nematostella vectensis , the assembled complex accelerates the larvae‐to‐adult metamorphosis process, further underscoring its multifaceted role and species‐specific action in diverse biological systems and ultimately paving the way for innovative theranostic strategies.

Breast cancer (BC) is the second most common noncutaneous cancer and the second leading cause of cancer-related death in women. BC is classified into three primary subtypes, with triple-negative breast cancer (TNBC) having the poorest prognosis because it lacks specific targetable markers. Preclinical studies on TNBC indicated a common occurrence of diminished tumor-suppressor activity of PTEN, activating the PI3K/AKT/mTOR signaling pathway. Notably, published studies reveal that the WWP1 enzyme plays a pivotal role in driving PTEN degradation via ubiquitination, unveiling a promising therapeutic target for treating TNBC. In the search of new WWP1 inhibitors, we used artificial intelligence (AI)-driven computational strategies for de novo design of peptide-based WWP1 inhibitors and identified a hexapeptide, termed WI23-B , which demonstrated high nanomolar binding affinity to WWP1. In TR-FRET enzymatic assays, WI23-B inhibited WWP1 activity with an IC₅₀ of approximately 11 µM. In MCF7 and MDA-MB-231 breast cancer cell lines, WI23-B showed promising cytotoxic efficacy, particularly in combination with the PI3K inhibitor BYL719, also when it was loaded into nanocapsules. Collectively, these findings highlight WI23-B as a promising lead peptide with potent WWP1 inhibitory activity and synergistic antiproliferative effects when combined with PI3K inhibitors. While further structural optimization is required to enhance its potency and pharmacological properties, our results provide a strong foundation for the development of next-generation WWP1 inhibitors. Such agents have the potential to reshape therapeutic strategies for BC and TNBC by enabling more effective and less toxic treatment regimens, ultimately reducing the reliance on high-dose chemotherapy and minimizing adverse effects.

High‐mobility group box 1 (HMGB1) is a protein acting as a regulator in tumor progression and therapy resistance, including breast cancer. HBP08‐2, a novel HMGB1‐inhibiting peptide, showed promising therapeutic potential; however, its poor stability and susceptibility to degradation limit cellular uptake. To overcome these limitations, a nanotechnology‐based delivery system was developed using breakable organosilica nanocapsules designed to degrade under reducing intracellular conditions. Nanocapsules were synthesized through a microemulsion‐assisted Stöber method and characterized by dynamic light scattering, transmission electron microscopy, and peptide quantification. They exhibited an encapsulation efficiency of 15.6%, a peptide content of 0.031 mg per mg of nanocapsules, and an average diameter of about 60 nm. In vitro studies demonstrated efficient internalization in MCF‐7 and MDA‐MB‐231 breast cancer cells, with >99% sulfo‐Cy5‐positive cells after 3 and 6 h. Empty nanocapsules were nontoxic and biocompatible, while HBP08‐2‐loaded nanocapsules reduced cell viability by approximately 30% after 96 h. Coadministration with paclitaxel (PTX), a first‐line chemotherapeutic, further enhanced the effect, reducing viability by up to 46.0% in MCF‐7 and 43.4% in MDA‐MB‐231, suggesting that the combination of HBP08‐2@CAPS and PTX may enhance cytotoxic activity compared with individual treatments. These findings support nanocapsules as a safe and versatile platform for intracellular peptide delivery and HMGB1‐targeted strategies.

Gold nanoparticles (AuNPs) have attracted considerable interest for biomedical applications due to their biocompatibility, tunable physicochemical properties, and potential for surface functionalization. In this study, purified Brazilian red propolis (RP) was employed as both reducing and stabilizing agent for the green synthesis of AuNPs. Initially, RP was characterized by total polyphenol content, antioxidant activity, Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). AuNPs were synthesized at pH 7.0 and 12.0 and characterized by ultraviolet‐visible (UV–vis) spectroscopy, dynamic light scattering (DLS), zeta potential (ZP) measurements, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and small‐angle x‐ray scattering. The synthesized NPs exhibited a characteristic band at 540 nm and predominantly spherical morphology, with particle sizes ranging from 5 to 20 nm. AuNPs synthesized at pH 7.0 displayed more favorable physicochemical characteristics, including a narrower LSPR band and improved colloidal behavior. The biological activity of purified RP, citrate‐stabilized (CS) AuNPs, and RP‐functionalized AuNPs was evaluated in colorectal cancer (HCT‐116) and non‐tumor fibroblast (L929) cell lines. RP‐functionalized AuNPs significantly reduced HCT‐116 cell viability after 24, 48, and 72 h of exposure while maintaining high cytocompatibility toward L929 cells, indicating a selective biological response. These findings highlight the potential of purified RP‐mediated AuNPs as promising nanoplatforms for biomedical applications.

Three injectable gelatin–PEG hydrogels (gelation: 1–2 min) were synthesized via radical polymerization mediated by cytochrome C. The hydrogels showed biocompatibility, biodegradability and sustained release of a drug-mimicking compound.

Small molecules may play a significant role as theranostic agents for the diagnosis and treatment of some severe disorders, such as cancer. A theranostic agent must have a therapeutic moiety, an imaging group for diagnostics, and a targeting portion for specific cell recognition. In this study, we synthesized two new molecules, D and E, as potential theranostic agents, consisting of a β-lactam portion acting as a selective α₄β₁ integrin agonist, a fluorescent imaging probe for diagnostics purposes, and a cytotoxic portion for anticancer activity. Compound D incorporates a 1,8-naphthylimide fluorophore for imaging and the 5-FU cytotoxic unit, whereas compound E features BODIPY moiety serving both as a photosensitizer and as a cytotoxic agent. Both compounds were evaluated for their photophysical properties. The binding assays for α₄β₁ integrin revealed that only E had a good affinity (K_D 68.2 ± 1.0 μM). In adhesion assays with Jurkat E6.1, K562, HT-29, and HEK-293 cells, E retained the selective agonist activity for α₄β₁ integrin (EC₅₀ 0.92 ± 0.14 μM) as the parental β-lactam ligand A. Upon photosensitization, compound E induced a significant concentration-dependent reduction in cell viability across all tested cell lines, regardless of integrin expression. Internalization experiments indicated a nonselective cellular uptake of compound E, likely due to its high lipophilicity, which may outweigh the contribution of structural elements responsible for specific integrin recognition.

Microporous annealed particle (MAP) scaffolds composed of cross-linked microgels are emerging as important biomaterials due to their modular design, high porosity, and large surface area, which allow for highly tailored properties, cellular infiltration, nutrient and waste exchange, and improved drug release characteristics. To further expand on these technologies and enhance their modular design, thiolated mesoporous organosilica nanoparticles (ssMSN-SH), which degrade in response to glutathione, were first cross-linked inside of 4-arm poly­(ethylene glycol) maleimide microgels. The microgel size, rheological properties, and payload release characteristics were determined. Hierarchical MAP scaffolds were then created by cross-linking 4-arm poly­(ethylene glycol) maleimide microgels with ssMSN-SH. Surface attachment and cross-linking of microgels using ssMSN-SH were confirmed with scanning electron microscopy and confocal imaging; rheological properties were characterized; porosity was analyzed; glutathione-induced degradation of MAP scaffolds was determined; and the depth of viable NIH/3T3 fibroblasts into MAP scaffolds was visualized using confocal microscopy. ssMSN-SH cross-linked microgels form MAP scaffolds with an increase in the storage modulus, maintain their porosity while decreasing the interparticle distance, degrade in response to glutathione, and increase the depth of viable NIH/3T3 fibroblasts into scaffolds when compared with bulk PEG hydrogels.

Although widely used in clinical diagnostics, the sensitivity of electrochemiluminescence (ECL) bead-based immunoassays is intrinsically limited by the reaction mechanism driving the emission of [Ru(bpy)₃]²⁺ on the bead surface. Depending mostly on the coreactant oxidation, the 'remote' pathway is hindered by the slow coreactant oxidation rate and the short half-lives of electrogenerated radicals. In this work, we synthesized a [Ru(bpy)₃]²⁺ derivative featuring a stimuli-responsive disulfide bond in its linker to the bead. Electrogenerated tri-n-propylamine (TPrA) neutral radicals reduce disulfide moieties, electrochemically inducing the release of Ru(II) labels in solution and thereby leading to an unprecedented mechanism shift toward the more efficient "homogeneous" ECL pathway. Leveraging ICP-MS, ECL microscopy, and finite element simulations, we demonstrate rapid bond cleavage and an impressive signal enhancement of up to 613%. Using an experimental configuration designed to emulate commercial clinical analysis, we developed an ECL-based immunoassay for the rapid detection of the SARS-CoV-2 Spike (S) protein in whole virus samples from swab formulations. The immunosensor incorporating the cleavable luminophore demonstrated a 40% lower detection limit and a 2-fold increase in sensitivity, while reducing TPrA consumption by 72%. These findings establish stimuli-responsive luminophores as a groundbreaking class of ECL labels, promising substantial improvements in the sensitivity of commercial biosensors.