Hyaluronic acid tethered pH-responsive alloy-drug nanoconjugates for multimodal therapy of glioblastoma: An intranasal route approach
Autor: | Kirti V. Patel, Abhijeet Pandey, Rajesh Singh, Kritarth Singh, Krutika K. Sawant, Sagar P. Patel |
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Rok vydání: | 2019 |
Předmět: |
Male
Swine Nanoconjugates 02 engineering and technology 01 natural sciences chemistry.chemical_compound Spectroscopy Fourier Transform Infrared Hyaluronic acid Hyaluronic Acid Internalization Lenalidomide media_common Photoelectron Spectroscopy Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Endocytosis Blood-Brain Barrier Mechanics of Materials Triethoxysilane 0210 nano-technology Materials science Cell Survival Iron media_common.quotation_subject Bioengineering Conjugated system 010402 general chemistry Biomaterials Dogs In vivo Cell Line Tumor Alloys Animals Humans Rats Wistar Administration Intranasal Platinum Mucins Hyperthermia Induced Phototherapy Photothermal therapy 0104 chemical sciences Drug Liberation Lactoferrin chemistry Biophysics Surface modification Glioblastoma Reactive Oxygen Species Oleic Acid |
Zdroj: | Materials Science and Engineering: C. 98:419-436 |
ISSN: | 0928-4931 |
Popis: | In the present investigation, FePt alloy nanoparticles were synthesized with controlled size and elemental composition followed by surface modification using (3-Aminopropyl) triethoxysilane (APTES). Lenalidomide was covalently bound to FePt-NH2 by pH sensitive hydrazone bonding. Hyaluronic acid was conjugated to amino groups of APTES while lactoferrin (Lf) was directly conjugated to excess carboxylic group present on hyaluronic acid (HA) to form surface modified pH sensitive alloy-drug nanoconjugates (SPANs). The multifunctional nanoconjugates were characterized and evaluated using extensive in vitro and in vivo techniques. The nanoconjugates demonstrated excellent heating ability on exposure to alternating magnetic field and near-infrared laser irradiation. The acidic microenvironment of lysozome triggered release of LND from SPANs. Owing to leaching of Fe and Pt contents, SPANs demonstrated ability to generate reactive oxygen species (ROS) in U87MG cell line which further enhanced therapeutic effect of SPANs. Significant difference in cell viability suppression was observed in in vitro photothermal, chemo-photothermal and chemo-magnetophotothermal killing of cancer cells using SPANs in U87MG cell lines. Significant difference in heating ability and cell cytotoxicity of SPANs in comparison to alternative magnetic field and NIR irradiation was observed for DUAL-mode exposure of SPANs. The results of cellular internalization study showed efficient internalization of SPANs inside U87MG cells. The in vivo results (both qualitative and quantitative) confirmed enhanced uptake of SPANs in brain after intranasal administration with enhanced nasal and mucus penetration owing to presence of Lf. No significant interaction was observed with ECM and mucin due to presence of carboxyl group on SPANs. |
Databáze: | OpenAIRE |
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