AEROSOLIZED GOLD-NANODEVICES FOR THERANOSTIC LUNG DELIVERY

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Aerosolizable gold nano-in-micro dry powder formulations for theragnosis and lung delivery

Publication . 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 Aguiar

Functionalized 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.

2017-01-19Journal article

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Design of oligoaziridine-PEG coatings for efficient nanogold cellular biotagging

Publication . Silva, A. Sofia; Bonifácio, Vasco; Raje, Vivek; Branco, Paula S.; Machado, Paulo Filipe Brito; Correia, Ilídio Joaquim Sobreira; Ricardo, Ana Aguiar

Gold nanoparticles (AuNPs) are the most investigated nanomaterials for theragnosis applications. In a research field where live cell assays, as well as the tracking of nanomaterials into a cell's environment, are of extremely importance, water-soluble AuNPs have been intensively studied to overcome the toxic effects exerted by coatings. Unfortunately, AuNPs fluorescent tagging often fails due to self-quenching and a careful design must be carried out to maintain optoelectronic properties and biocompatibility. In this work, the synthesis of fluorescent gold nanoprobes, able to enter the cell's environment (biotags) and target the cell nucleus, was designed and the particles tracked by confocal laser scanning microscopy. The coating of AuNPs with maleimide poly(ethylene glycol) and fluorescent oligoaziridine biocompatible oligomers, resulted in robust, optically active biotags that open novel insights into cancer theragnosis.

2015-01-07Journal article

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Novel Methodology Based on Biomimetic Superhydrophobic Substrates to Immobilize Cells and Proteins in Hydrogel Spheres for Applications in Bone Regeneration

Publication . Lima, Ana; Batista, Patrícia Sofia Pinhanços; Valente, Tiago António Martins; Silva, A. Sofia; Correia, Ilídio Joaquim Sobreira; Mano, João

Cell-based therapies for regenerative medicine have been characterized by the low retention and integration of injected cells into host structures. Cell immobilization in hydrogels for target cell delivery has been developed to circumvent this issue. In this work mesenchymal stem cells isolated from Wistar rats bone marrow (rMSCs) were immobilized in alginate beads fabricated using an innovative approach involving the gellification of the liquid precursor droplets onto biomimetic superhydrophobic surfaces without the need of any precipitation bath. The process occurred in mild conditions preventing the loss of cell viability. Furthermore, fibronectin (FN) was also immobilized inside alginate beads with high efficiency in order to mimic the composition of the extracellular matrix. This process occurred in a very fast way (around 5 min), at room temperature, without aggressive mechanical strengths or particle aggregation. The methodology employed allowed the production of alginate beads exhibiting a homogenous rMSCs and FN distribution. Encapsulated rMSCs remained viable and were released from the alginate for more than 20 days. In vivo assays were also performed, by implanting these particles in a calvarial bone defect to evaluate their potential for bone tissue regeneration. Microcomputed tomography and histological analysis results showed that this hybrid system accelerated bone regeneration process. The methodology employed had a dual role by preventing cell and FN loss and avoiding any contamination of the beads or exchange of molecules with the surrounding environment. In principle, the method used for cell encapsulation could be extended to other systems aimed to be used in tissue regeneration strategies.

2013-02-14Journal article

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