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
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