@misc{10481/97051,
year = {2024},
month = {11},
url = {https://hdl.handle.net/10481/97051},
abstract = {Background/Objectives: The development of therapies targeting unregulated Src signaling
through selective kinase inhibition using small-molecule inhibitors presents a significant challenge
for the scientific community. Among these inhibitors, pyrazolo[3,4-d]pyrimidine heterocycles have
emerged as potent agents; however, their clinical application is hindered by low solubility in water.
To overcome this limitation, some carrier systems, such as halloysite nanotubes (HNTs), can be used.
Methods: Herein, we report the development ofHNT-based nanomaterials as carriers for pyrazolo[3,4-
d]pyrimidine molecules. To achieve this objective, the clay was modified by two different approaches:
supramolecular loading into the HNT lumen and covalent grafting onto the HNT external surface.
The resulting nanomaterials were extensively characterized, and their morphology was imaged
by high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM). In
addition, the kinetic release of the molecules supramolecularly loaded into the HNTs was also
evaluated. QSAR studies were conducted to elucidate the physicochemical and pharmacokinetic
properties of these inhibitors, and structure-based virtual screening (SBVS) was performed to analyze
their binding poses in protein kinases implicated in cancer. Results: The characterization methods
demonstrate successful encapsulation of the drugs and the release properties under physiological
conditions. Furthermore, QSAR studies and SBVS provide valuable insights into the physicochemical,
pharmacokinetic, and binding properties of these inhibitors, reinforcing their potential efficacy.
Conclusions: The cytotoxicity of these halloysite-based nanomaterials, and of pure molecules for
comparison, was tested on RT112, UMUC3, and PC3 cancer cell lines, demonstrating their potential
as effective agents for prostate and bladder cancer treatment.},
organization = {Avviso n.6/2022 “Rafforzamento del sistema di ricerca universitario in Sicilia
mediante azioni di reclutamento a tempo determinato” UNIPA—CUP: G71I22000950001 of Regione
Siciliana},
organization = {National Recovery and Resilience Plan (NRRP), funded by the European Union–
NextGenerationEU-DD 1409 Progetti di Rilevante InteresseNazionale (PRIN) 2022 PNRR},
organization = {Investment
1.1.Project Title: Small Molecule Anticancer Ligands Library from mediterranean plants (SMALL)–
CUPB53D23025910001.–Code P2022YJZ5F},
publisher = {MDPI},
keywords = {pyrazolo[3,4-d]pyrimidine derivatives},
keywords = {halloysite},
keywords = {carrier},
title = {Halloysite Nanotube-Based Delivery of Pyrazolo[3,4-d]pyrimidine Derivatives for Prostate and Bladder Cancer Treatment},
doi = {10.3390/pharmaceutics16111428},
author = {Massaro, Marina and Ciani, Rebecca and Grossi, Giancarlo and Cavallaro, Gianfranco and de Melo Barbosa, Raquel and Falesiedi, Marta and Fortuna, Cosimo Gianluca and Carbone, Anna and Schenone, Silvia and Sánchez Espejo, Rita María and Viseras Iborra, César Antonio and Vago, Riccardo and Riela, Serena},
}