RESUMO
Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early diagnosis, efficient prevention and therapy without toxicity. Yet, in spite of 25 years of research, there are still no such shuttles available. To this end, we have designed magnetic and gold nanoparticles (NP)-embedded silica nanoshuttles (MGNSs) with nanopores on their surface. Fluorescently labeled Doxorubicin (DOX), a cancer drug, was loaded in the MGNSs as a payload. DOX loaded MGNSs were encapsulated in heat and pH sensitive polymer P(NIPAM-co-MAA) to enable controlled release of the payload. Magnetically-guided transport of MGNSs was examined in: (a) a glass capillary tube to simulate their delivery via blood vessels; and (b) porous hydrogels to simulate their transport in composite human tissues, including bone, cartilage, tendon, muscles and blood-brain barrier (BBB). The viscoelastic properties of hydrogels were examined by atomic force microscopy (AFM). Cellular uptake of DOX-loaded MGNSs and the subsequent pH and temperature-mediated release were demonstrated in differentiated human neurons derived from induced pluripotent stem cells (iPSCs) as well as epithelial HeLa cells. The presence of embedded iron and gold NPs in silica shells and polymer-coating are supported by SEM and TEM. Fluorescence spectroscopy and microscopy documented DOX loading in the MGNSs. Time-dependent transport of MGNSs guided by an external magnetic field was observed in both glass capillary tubes and in the porous hydrogel. AFM results affirmed that the stiffness of the hydrogels model the rigidity range from soft tissues to bone. pH and temperature-dependent drug release analysis showed stimuli responsive and gradual drug release. Cells' viability MTT assays showed that MGNSs are non-toxic. The cell death from on-demand DOX release was observed in both neurons and epithelial cells even though the drug release efficiency was higher in neurons. Therefore, development of smart nanoshuttles have significant translational potential for controlled delivery of theranostics' payloads and precisely guided transport in specified tissues and organs (for example, bone, cartilage, tendon, bone marrow, heart, lung, liver, kidney, and brain) for highly efficient personalized medicine applications.
RESUMO
Hybrid nanocarriers with multifunctional properties have wide therapeutic and diagnostic applications. We have constructed hollow silica nanogolf balls (HGBs) and gold-embedded hollow silica nanogolf balls (Au@SiO2 HGBs) using the layer-by-layer approach on a symmetric polystyrene (PS) Janus template; the template consists of smaller PS spheres attached to an oppositely charged large PS core. ζ Potential measurement supports the electric force-based template-assisted synthesis mechanism. Electron microscopy, UV-vis, and near-infrared (NIR) spectroscopy show that HGBs or Au@SiO2 HGBs are composed of a porous silica shell with an optional dense layer of gold nanoparticles embedded in the silica shell. To visualize their cellular uptake and imaging potential, Au@SiO2 HGBs were loaded with quantum dots (QDs). Confocal fluorescent microscopy and atomic force microscopy imaging show reliable endocytosis of QD-loaded Au@SiO2 HGBs in adherent HeLa cells and circulating red blood cells (RBCs). Surface-enhanced Raman spectroscopy of Au@SiO2 HGBs in RBC cells show enhanced intensity of the Raman signal specific to the RBCs' membrane specific spectral markers. Au@SiO2 HGBs show localized surface plasmon resonance and heat-induced HeLa cell death in the NIR range. These hybrid golf ball nanocarriers would have broad applications in personalized nanomedicine ranging from in vivo imaging to photothermal therapy.
