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- Aerosolizable gold nano-in-micro dry powder formulations for theragnosis and lung deliveryPublication . Silva, A. Sofia; Sousa, Ana M. L.; Cabral, Renato; Silva, Marta; Sequeira, Clarinda Costa; Miguel, Sónia; Bonifácio, Vasco; Casimiro, Teresa; Correia, I.J.; Ricardo, Ana AguiarFunctionalized gold nanoparticles (AuNPs) have been widely investigated as promising multifunctional nanosystems for the theragnosis of lung cancer, the most common and prominent cause of cancer death worldwide. Nevertheless, nanoparticles are not in appropriate sizes for an accurate deep lung delivery and the lack of locally and effective delivery of therapeutic biomolecules to the deep lungs is, in fact, the major cause of low therapeutic outcome. Herein we incorporate, for the first time, AuNPs into respirable microparticles. AuNPs were functionalized with biocompatible oligo(2-oxazoline)-based optically stable fluorescent coatings, and conjugated with a laminin peptide (YIGSR) for targeted lung cancer delivery. These POxylated AuNPs were then incorporated into a chitosan matrix by a clean process, supercritical CO2-assisted spray drying (SASD), yielding nano-in-micro clean ultrafine dry powder formulations. The engineered formulations present the adequate morphology and flowability to reach the deep lung, with aerodynamic sizes ranging 3.2–3.8 μm, and excellent fine particle fraction (FPF) (FPF of 47% for CHT-bearing targeted AuNPs). The optimal biodegradation and release profiles enabled a sustained and controlled release of the embedded nanoparticles, with enhanced cellular uptake, opening new prospects for future lung theragnosis.
- Nanogold POxylation: towards always-on fluorescent lung cancer targetingPublication . Silva, A. Sofia; Silva, Marta; Miguel, Sónia P.; Bonifácio, Vasco; Correia, Ilídio Joaquim Sobreira; Ricardo, Ana AguiarGold nanoparticles (GNPs) are one of most investigated nanomaterials for lung cancer diagnosis and therapy (theragnosis). For imaging purposes, GNPs are often tagged with fluorescent probes, but unfortunately the associated plasmon resonance effect leads to fluorescence self-quenching, thus precluding accurate localization. In this study, biocompatible GNPs targeted with a laminin fragment were successfully engineered using fluorescent oligo-oxazolines produced in supercritical carbon dioxide. The architecture and properties of the POxylated constructs were fully characterized and confocal laser scanning microscopy measurements demonstrated a higher cellular uptake into A549 lung cancer cells through an active targeting mechanism.