Halloysite Nanotube-Based Delivery of Pyrazolo[3,4-<i>d</i>]pyrimidine Derivatives for Prostate and Bladder Cancer Treatment
Marina Massaro,
Rebecca Ciani,
Giancarlo Grossi,
Gianfranco Cavallaro,
Raquel de Melo Barbosa,
Marta Falesiedi,
Cosimo G. Fortuna,
Anna Carbone,
Silvia Schenone,
Rita Sánchez-Espejo,
César Viseras,
Riccardo Vago,
Serena Riela
Affiliations
Marina Massaro
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Viale delle Scienze, Parco d’Orleans II, Ed. 17, 90128 Palermo, Italy
Rebecca Ciani
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Viale delle Scienze, Parco d’Orleans II, Ed. 17, 90128 Palermo, Italy
Giancarlo Grossi
Department of Pharmacy, University of Genoa, Viale Benedetto XV, 16132 Genoa, Italy
Gianfranco Cavallaro
Dipartimento di Scienze Chimiche (DSC), Università di Catania, Viale Andrea Doria 6, 95125 Catania, Italy
Raquel de Melo Barbosa
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Seville, C/Professor García González 2, 41012 Sevilla, Spain
Marta Falesiedi
Department of Pharmacy, University of Genoa, Viale Benedetto XV, 16132 Genoa, Italy
Cosimo G. Fortuna
Dipartimento di Scienze Chimiche (DSC), Università di Catania, Viale Andrea Doria 6, 95125 Catania, Italy
Anna Carbone
Department of Pharmacy, University of Genoa, Viale Benedetto XV, 16132 Genoa, Italy
Silvia Schenone
Department of Pharmacy, University of Genoa, Viale Benedetto XV, 16132 Genoa, Italy
Rita Sánchez-Espejo
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, 18071 Granada, Spain
César Viseras
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, 18071 Granada, Spain
Riccardo Vago
Istituto San Raffaele (IRCCS), Istituto di Ricerca Urologica, Divisione di Oncologia Sperimentale, 20132 Milano, Italy
Serena Riela
Dipartimento di Scienze Chimiche (DSC), Università di Catania, Viale Andrea Doria 6, 95125 Catania, Italy
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 of HNT-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.
