ABSTRACT
Osteoarthritis (OA) is the most common form of arthritis, with intra-articular (IA) delivery of therapeutics being the current best option to treat pain and inflammation. However, IA delivery is challenging due to the rapid clearance of therapeutics from the joint and the need for repeated injections. Thus, there is a need for long-acting delivery systems that increase the drug retention time in joints with the capacity to penetrate OA cartilage. As pharmaceutical utility also demands that this is achieved using biocompatible materials that provide colloidal stability, our aim was to develop a nanoparticle (NP) delivery system loaded with the COX-2 inhibitor celecoxib that can meet these criteria. We devised a reproducible and economical method to synthesize the colloidally stable albumin NPs loaded with celecoxib without the use of any of the following conditions: high temperatures at which albumin denaturation occurs, polymer coatings, oils, Class 1/2 solvents, and chemical protein cross-linkers. The spherical NP suspensions were biocompatible, monodisperse with average diameters of 72 nm (ideal for OA cartilage penetration), and they were stable over 6 months at 4 °C. Moreover, the NPs loaded celecoxib at higher levels than those required for the therapeutic response in arthritic joints. For these reasons, they are the first of their kind. Labeled NPs were internalized by primary human articular chondrocytes cultured from the knee joints of OA patients. The NPs reduced the concentration of inflammatory mediator prostaglandin E2 released by the primaries, an indication of retained bioactivity following NP synthesis. Similar results were observed in lipopolysaccharide-stimulated human THP-1 monocytes. The IA administration of these NPs is expected to avoid side-effects associated with oral administration of celecoxib and to maintain a high local concentration in the knee joint over a sustained period. They are now ready for evaluation by IA administration in animal models of OA.
Subject(s)
Nanoparticles , Osteoarthritis , Animals , Humans , Celecoxib/pharmacology , Celecoxib/therapeutic use , Injections, Intra-Articular , Osteoarthritis/drug therapy , Knee Joint , AlbuminsABSTRACT
We report a simple approach for fabricating plasmonic and magneto-luminescent multifunctional nanocarriers (MFNCs) by assembling gold nanorods, iron oxide nanoparticles, and gold nanoclusters within BSA nanoparticles. The MFNCs showed self-tracking capability through single- and two-photon imaging, and the potential for magnetic targeting in vitro. Appreciable T2-relaxivity exhibited by the MFNCs indicated favorable conditions for magnetic resonance imaging. In addition to successful plasmonic-photothermal therapy of cancer cells (HeLa) in vitro, the MFNCs demonstrated efficient loading and delivery of doxorubicin to HeLa cells leading to significant cell death. The present MFNCs with their multimodal imaging and therapeutic capabilities could be eminent candidates for cancer theranostics.
Subject(s)
Nanostructures , Antineoplastic Agents , Doxorubicin , Drug Delivery Systems , HeLa Cells , Humans , Magnetic Resonance Imaging , Theranostic NanomedicineABSTRACT
We report the synthesis of a biofriendly highly luminescent white-light-emitting nanocomposite. The composite consisted of Au nanoclusters and ZnQ2 complex (on the surface of ZnS quantum dots) embedded in protein. The combination of red, green, and blue luminescence from clusters, complex, and protein, respectively, led to white light generation.
Subject(s)
Gold/chemistry , Light , Nanocomposites/chemistry , Quantum Dots/chemistry , Serum Albumin, Bovine/metabolism , Animals , Cattle , Cell Survival , HEK293 Cells , Humans , Spectrometry, FluorescenceABSTRACT
We report the synthesis of a magnetofluorescent biocompatible nanoprobe-following room temperature complexation reaction between Fe3O4-ZnS nanocomposite and 8-hydroxyquinoline (HQ). The composite nanoprobe exhibited high luminescence quantum yield, low rate of photobleaching, reasonable excited-state lifetime, luminescence stability especially in human blood serum, superparamagnetism and no apparent cytotoxicity. Moreover, the nanoprobe could be used for spatio-controlled cell labeling in the presence of an external magnetic field. The ease of synthesis and cell labeling in vitro make it a suitable candidate for targeted bioimaging applications.
Subject(s)
Biocompatible Materials/chemistry , Fluorescent Dyes/chemistry , Magnetite Nanoparticles/chemistry , Ferrosoferric Oxide/chemistry , HeLa Cells , Humans , Magnetics , Magnetite Nanoparticles/ultrastructure , Microscopy, Confocal , Oxyquinoline/chemistry , Quantum Dots/chemistry , Quantum Theory , Spectroscopy, Fourier Transform Infrared , Sulfides/chemistry , Ultraviolet Rays , Zinc Compounds/chemistryABSTRACT
Gold nanoclusters in albumin nanoparticles (nanovehicles) are used for single-photon and two-photon imaging of cancer cells following the delivery of doxorubicin through the nanovehicle. NIR excitation and emission wavelengths in the biological window (650-900 nm) make the nanovehicle an ideal potential platform for imaging guided drug delivery.
Subject(s)
Albumins/chemistry , Doxorubicin/administration & dosage , Gold/chemistry , Metal Nanoparticles/chemistry , Neoplasms/diagnosis , Neoplasms/drug therapy , Albumins/administration & dosage , Antineoplastic Agents/administration & dosage , Diagnostic Imaging/methods , Drug Delivery Systems/methods , HeLa Cells , Humans , Neoplasms/pathology , Optical Imaging/methods , Photons , Spectroscopy, Near-InfraredABSTRACT
Polymer coated gold nanoparticle-protein agglomerates having excellent protease and human blood serum stability are reported. These biocompatible agglomerates served as nanocarriers (NCs) for the hydrophobic anticancer drug camptothecin. The NCs were fabricated based on non-covalent interactions and meet the size criterion for extravasation through the leaky vessels of tumor vasculature. The camptothecin loaded NCs were internalized by human cervical cancer HeLa cells, thereby releasing their payloads and causing apoptotic cell death. These NCs have the potential for use in clinical applications.
ABSTRACT
The fabrication of a versatile nanocarrier based on agglomerated structures of gold nanoparticle (Au NP)-lysozyme (Lyz) in aqueous medium is reported. The carriers exhibit efficient loading capacities for both hydrophilic (doxorubicin) and hydrophobic (pyrene) molecules. The nanocarriers are finally coated with an albumin layer to render them stable and also facilitate their uptake by cancer cells. The interaction between agglomerated structures and the payloads is non-covalent. Cell viability assay in vitro showed that the nanocarriers by themselves are non-cytotoxic, whereas the doxorubicin-loaded ones are cytotoxic, with efficiencies higher than that of the free drug. Transmission electron microscopy and fluorescence microscopy along with flow cytometry analysis confirm the uptake of the drug-loaded nanocarriers by a human cervical cancer HeLa cell line. Field-emission scanning electron microscopy reveals the formation of apoptotic bodies leading to cell death, confirming the release of the payloads from the nanocarriers into the cell. Overall, the findings suggest the fabrication of novel Au NP-protein agglomerate-based nanocarriers with efficient drug-loading and -releasing capabilities, enabling them to act as multimodal drug-delivery vehicles.
