Grazia Maria Letizia Consoli

Fluorescence imaging techniques are emerging as safer and more sensitive alternatives to radionuclide-based approaches for cancer diagnosis. Entrapping fluorophores that also act as photosensitizers within nanocarriers is an effective strategy to enhance their stability, performance, and selective delivery to tumor tissues, enabling the development of advanced nanosystems for cancer cell imaging and theranostic applications. In this work, we report a fluorescent nanosystem obtained by entrapping Coumarin 6 in biocompatible nanostructures formed through the self-assembly of an amphiphilic calix[4]­arene derivative functionalized with choline ligands for targeting tumor cells. The nanosystem was characterized using diverse techniques, which confirmed nanoscale organization, colloidal stability, excellent resistance to freeze-drying, good fluorescence quantum yield, and visible-light-triggered photodynamic activity, as evidenced by methylene blue photodegradation. Molecular modeling simulations provided mechanistic insight into the host–guest interactions governing Coumarin 6 stabilization in the nanocarrier. The nanosystem selectively imaged breast carcinoma (MCF-7 and MDA-MB-231) and hepatocarcinoma (Hep3B and SNU398) cells that overexpress the choline transporter, while negligible uptake was observed in nonmalignant human fibroblasts (HuDe cells). Intracellular fluorescence intensity correlated with choline transporter expression levels, and the competitive inhibition assay supported a transporter-mediated cellular uptake mechanism. Upon biocompatible visible-light irradiation, the nanosystem effectively induced cancer cell death through activation of the Coumarin 6 photosensitizer. The integration of targeted cancer cell imaging and phototriggered cytotoxicity highlights this fluorescent nanosystem as a promising photoresponsive nanotheranostic candidate.

Carbon nanodots (CDs) are an emerging class of nanomaterials that have recently attracted significant attention for applications in personalized diagnosis, therapy and theragnostics.

Calix[ n ]arenes are polyphenolic macrocycles known for their remarkable synthetic versatility, which supports their broad application in various areas, including drug discovery. Their unique conformational features, functionality, and low toxicity make calixarene derivatives valuable drug candidates against cancer. The aim of the present study was the synthesis and characterization of a calix[4]arene derivative in which known anticancer isothiouronium groups were clustered on a calix[4]arene scaffold bearing long C12 alkyl chains at the lower rim. The resulting amphiphilic calix[4]arene derivative 3 spontaneously self-assembled into nanoscale aggregates in aqueous medium, as demonstrated by dynamic light scattering analysis. The cytotoxicity of compound 3 towards cancer cells was assessed using human renal carcinoma cells (786-O cells) and compared with that in non-malignant fibroblast cells (SW1 cells). Compound 3 showed a significantly greater antiproliferative effect on cancer cells (IC ₅₀ 37.4 µM) than on normal fibroblasts (517 µM). The importance of the isothiouronium moieties in the observed cytoxic effect was confirmed by comparison with the calix[4]arene precursor ( 1 ) lacking these functional units. The selective antiproliferative profile of compound 3 highlights its potential as a lead anticancer agent. Moreover, compound 3 holds promise for further development in combination multidrug therapy due to the potential to load drug molecules in the bioactive nanoassembled structure.

Thermoresponsive CDs–agar–PNM nanocomposites integrate photothermal carbon dots and PNIPAM–agarose shells, exhibiting tunable LCST behavior, efficient light heating, and temperature-controlled curcumin release for biomedical applications.

Resveratrol is one of the most extensively studied natural products due to its pleiotropic health benefits. However, its low water solubility and limited stability hinder its application in the nutraceutical, cosmetic, and pharmaceutical sectors. In this work, we investigated the ability of a cationic mono-choline-β-cyclodextrin derivative to complex trans-resveratrol. The complex was prepared using a phase solubility method without using organic solvents and was found to be stable after freeze-drying. The complex was characterized by a phase solubility study, NMR spectroscopy, and molecular modeling simulations, which revealed a 1:1 stoichiometry, a stability constant of 2051 M⁻¹ (K_C), and structural details. Complexation improved resveratrol’s solubility and dissolution rate, reduced its photoinduced trans-to-cis isomerization, and preserved its radical scavenging activity. The wound-healing activity of the complex was demonstrated via in vitro experiments on human keratinocyte cells.

We have designed and synthesized a novel calix[4]arene derivative bearing four choline appendages as recognition targeting ligands and one amino-nitrobenzofurazan as a fluorescent labelling unit at the opposite sides of the calixarene molecular scaffold. Due to its amphiphilic character, this compound is well soluble in water, forming supramolecular assemblies that are ca. 170 nm in diameter. The nanoassembly selectively targets cancer cells that overexpress the choline transporters, and it can be visualized thanks to the fluorescent tag. The fluorogenic unit also acts as a green light harvesting center, making the nanoassembly a photo-nanoreactor able to encapsulate a hydrophobic nitric oxide (NO) photodonor, otherwise activatable with blue light, and encouraging the NO release with the more biocompatible green light probably by an intra-cage photoinduced electron transfer.

Background: The design of multifunctional carbon based nanosystems exhibiting light-triggered hyperthermia, emission, low cytotoxicity, and drug delivery capability is of significant interest in the area of nanomaterials. In this study, we present red-emitting and photothermal carbon nanodots (Cdots-βCD/PTC) obtained by the encapsulation of hydrophobic pentacene (PTC) within Carbon nanodots (Cdots) synthesized from beta-cyclodextrin (βCD). Methods: The prepared nanostructures were investigated in terms of morphology, size, and optical properties, by absorption and emission optical spectroscopy, atomic force microscopy, dynamics light scattering, Z-potential, nuclear magnetic resonance, and infra-red spectroscopy. Molecular modelling simulation was used to investigate the geometry and the stabilization energy of the Cdots-βCD/PTC inclusion complex. Results: The as prepared Cdots-βCD/PTC demonstrated good water dispersibility, green-emission (ϕ_PL = 1.7%), and photothermal conversion (η = 17.4%) upon red-light excitation (680 nm). Furthermore, Cdots-βCD/PTC low cytotoxicity in the range 0.008 μg–0.8 μg and good interaction with albumin protein (K_SV = 2.78 ± 0.28 mL mg⁻¹) were demonstrated. Molecular simulation analysis revealed the formation of the inclusion complex with an energy of −5.32 kcal mol⁻¹, where PTC is orthogonally oriented in the βCD cavity. Conclusions: The results presented in this work highlight the potential of Cdots-βCD/PTC as a novel versatile nanosystem for biomedical applications, such as bioimaging and site-specific photothermal treatment of cancer cells.

We have designed and synthesized a novel calix[4]arene derivative bearing four choline appendages, as recognition targeting ligands, and one amino-nitrobenzofurazan, as a fluorescent labeling unit, at the opposite sides of the calixarene molecular scaffold. Due to its amphiphilic character, this compound is well soluble in water, forming supramolecular assemblies that are ca. 170 nm in diameter. The nanoassembly selectively targets cancer cells that overexpress the choline receptors, and it can be visualized thanks to the fluorescent tag. The fluorogenic unit also acts as a green light harvesting center, making the nanoassembly a photo-nanoreactor able to encapsulate a hydrophobic nitric oxide (NO) photodonor, otherwise activatable with blue light, and encouraging the NO release with the more biocompatible green light probably by an intra-cage photoinduced electron transfer.