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1.
Int J Biol Macromol ; 189: 443-454, 2021 Oct 31.
Article in English | MEDLINE | ID: mdl-34425122

ABSTRACT

In this contribution, we report the fabrication of multifunctional nanoparticles with gold shell over an iron oxide nanoparticles (INPs) core. The fabricated system combines the magnetic property of INPs and the surface plasmon resonance of gold. The developed nanoparticles are coated with thiolated pectin (TPGINs), which provides stability to the nanoparticles dispersion and allows the loading of hydrophobic anticancer drugs. Curcumin (Cur) is used as the model drug and an encapsulation efficiency of approximately 80% in TPGINs is observed. Cytotoxicity study with HeLa cells shows that Cur-loaded TPGINs have better viability percent (~30%) than Cur alone (~40%) at a dose of 30 µg of TPGINs. Further, annexin V-PI assay demonstrated the enhanced anticancer activity of Cur-loaded TPGINs via induction of apoptosis. The use of TPGINs leads to a significant enhancement in generating reactive oxygen species (ROS) in HeLa cells through improved radiosensitization by gamma irradiation (0.5 Gy). TPGINs are further evaluated for imparting contrast in magnetic resonance imaging (MRI) with the r2 relaxivity in the range of 11.06-13.94 s-1 µg-1 mL when measured at 7 Tesla. These experimental results indicate the potential of TPGINs for drug delivery and MR imaging.


Subject(s)
Diagnostic Imaging , Multifunctional Nanoparticles/chemistry , Neoplasms/diagnostic imaging , Neoplasms/therapy , Pectins/chemistry , Radiation Tolerance , Cell Death/drug effects , Cell Survival/drug effects , Curcumin/pharmacology , Drug Liberation , Endocytosis/drug effects , HeLa Cells , Humans , Hydrodynamics , Kinetics , Magnetic Resonance Imaging , Multifunctional Nanoparticles/ultrastructure , Particle Size , Phantoms, Imaging , Photoelectron Spectroscopy , Reactive Oxygen Species/metabolism , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , Spectrum Analysis, Raman , Staining and Labeling , Thermogravimetry
2.
Nanomedicine ; 32: 102325, 2021 02.
Article in English | MEDLINE | ID: mdl-33186695

ABSTRACT

Respiratory Syncytial Virus (RSV) has been a major health concern globally for decades, yet no effective prophylactic or treatment regimen is available. The key viral proteins responsible for RSV pathology include the fusion protein (F), the immunomodulatory non-structural-protein 1 (NS1) and the phosphoprotein (P) involved in viral replication. Herein, we developed a novel shell-core multifunctional nanosystem with dual payload: a plasmid construct encoding for shRNAs against NS1 and P, and an anti-fusion peptide (HR2D). Anti-ICAM1 antibody conjugated on the nanoparticle (NP) surface is used to target RSV infected cells. Our data show the potential of this nanosystem as a prophylactic and/or a therapeutic regimen against RSV infection. Furthermore, therapy of RSV infected mice with this nanosystem, in addition to reducing viral load, modulated expression of Th2 and allergy-associated cytokines such as IL4, IL-13 and IL-17 indicating a direct role of this nanosystem in the mechanisms involved in the immunoregulation of disease pathogenesis.


Subject(s)
Multifunctional Nanoparticles/therapeutic use , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus, Human/physiology , Animals , Cytokines/metabolism , Drug Liberation , Female , Inflammation Mediators/metabolism , Intercellular Adhesion Molecule-1/metabolism , Mice, Inbred BALB C , Multifunctional Nanoparticles/ultrastructure , Peptides/pharmacology , Plasmids/genetics , RNA, Small Interfering/metabolism , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Virus, Human/drug effects , Transfection , Viral Fusion Proteins/metabolism
3.
Sci Robot ; 5(42)2020 05 20.
Article in English | MEDLINE | ID: mdl-33022624

ABSTRACT

Mobile microrobots offer great promise for minimally invasive targeted medical theranostic applications at hard-to-access regions inside the human body. The circulatory system represents the ideal route for navigation; however, blood flow impairs propulsion of microrobots especially for the ones with overall sizes less than 10 micrometers. Moreover, cell- and tissue-specific targeting is required for efficient recognition of disease sites and long-term preservation of microrobots under dynamic flow conditions. Here, we report cell-sized multifunctional surface microrollers with ~3.0 and ~7.8-micrometer diameters, inspired by leukocytes in the circulatory system, for targeted drug delivery into specific cells and controlled navigation inside blood flow. The leukocyte-inspired spherical microrollers are composed of magnetically responsive Janus microparticles functionalized with targeting antibodies against cancer cells (anti-HER2) and light-cleavable cancer drug molecules (doxorubicin). Magnetic propulsion and steering of the microrollers resulted in translational motion speeds up to 600 micrometers per second, around 76 body lengths per second. Targeting cancer cells among a heterogeneous cell population was demonstrated by active propulsion and steering of the microrollers over the cell monolayers. The multifunctional microrollers were propelled against physiologically relevant blood flow (up to 2.5 dynes per square centimeter) on planar and endothelialized microchannels. Furthermore, the microrollers generated sufficient upstream propulsion to locomote on inclined three-dimensional surfaces in physiologically relevant blood flow. The multifunctional microroller platform described here presents a bioinspired approach toward in vivo controlled propulsion, navigation, and targeted active cargo delivery in the circulatory system.


Subject(s)
Drug Delivery Systems/instrumentation , Robotics/instrumentation , Antineoplastic Agents/administration & dosage , Biomimetic Materials , Cell Line, Tumor , Doxorubicin/administration & dosage , Equipment Design , Hemodynamics/physiology , Humans , Magnetics , Microtechnology/instrumentation , Motion , Multifunctional Nanoparticles/chemistry , Multifunctional Nanoparticles/ultrastructure , Precision Medicine/instrumentation , Surface Properties
4.
ACS Appl Mater Interfaces ; 12(7): 8351-8358, 2020 Feb 19.
Article in English | MEDLINE | ID: mdl-31965786

ABSTRACT

Using flexible structures and components of metal-organic framework (MOF) materials, we designed and developed an artificial nanozyme with dual functions of a catalyst and luminescent sensor specifically for the determination and degradation of hormone 17ß-estradiol (E2) and its derivatives (E1, E3, and EE2), a class of disruptors with strong effect on the human endocrine system. This nanozyme composed of the luminescent Tb3+ ion, catalytic coenzyme factor hemin, and light-harvesting ligand can be used to both degrade E2 like natural horseradish peroxidase (HRP) and sense E2 as low as 50 pM by its luminescence. The nanozyme catalyzes the decomposition of E2 and its derivatives through a mechanism of active hydroxyl radicals and oxidative high-valent iron-oxo intermediates. The prepared nanozyme is pluripotent, stable, and cheap and can replace the widely used combination of natural enzyme and chromogenic substrate. The present strategy of constructing artificial enzymes directly from functional units provides a new way for the design and development of smart, multifunctional artificial enzymes.


Subject(s)
Endocrine Disruptors/metabolism , Estradiol/chemistry , Hemin/chemistry , Metal-Organic Frameworks/chemistry , Multifunctional Nanoparticles/chemistry , Peroxidase/chemistry , Terbium/chemistry , Biomimetic Materials/chemistry , Catalysis , Estradiol/analogs & derivatives , Hydrogen Peroxide/chemistry , Kinetics , Ligands , Luminescence , Microscopy, Electron, Scanning , Multifunctional Nanoparticles/ultrastructure
5.
ACS Appl Mater Interfaces ; 12(7): 8392-8402, 2020 Feb 19.
Article in English | MEDLINE | ID: mdl-31971769

ABSTRACT

Mismatched deformation in a bilayer composite with rigid coating on a soft substrate results in complex and uniform topographic patterns, yet it remains challenging to heterogeneously pattern the upper coatings with various localized structures. Herein, a heterogeneous, 3D microstructure composed of Ti3C2Tx titanium carbide (MXene) and single-walled carbon nanotubes (SWNTs) was fabricated using a one-step deformation of a thermally responsive substrate with designed open holes. The mechanically deformed SWNT-MXene (s-MXene) structure was next transferred onto an elastomeric substrate, and the resulting s-MXene/elastomer bilayer device exhibited three localized surface patterns, including isotropic crumples, periodic wrinkles, and large papillae-like microstructures. By adjusting the number and pattern, the s-MXene papillae arrays exhibited superhydrophobicity (>170°), strong and tunable adhesive force (52.3-110.6 µN), and ultra-large liquid capacity (up to 35 µL) for programmable microdroplet manipulation. The electrically conductive nature of s-MXene further enabled proper thermal management on microdroplets via Joule heating for miniaturized antibacterial tests. The s-MXene papillae were further fabricated in a piezoresistive pressure sensor with high sensitivity (11.47 kPa-1). The output current changes of s-MXene sensors were highly sensitive to voice vibrations and responded identically with prerecorded profiles, promising their application in accurate voice acquisition and recognition.


Subject(s)
Multifunctional Nanoparticles/chemistry , Nanotubes, Carbon/chemistry , Stress, Mechanical , Titanium/chemistry , Elastomers/chemistry , Hydrophobic and Hydrophilic Interactions , Microscopy, Electron, Scanning , Multifunctional Nanoparticles/ultrastructure , Surface Properties , Temperature , Vibration , Voice
6.
Colloids Surf B Biointerfaces ; 183: 110429, 2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31426025

ABSTRACT

As a member of flavonoids, the application of quercetin has been mainly focused on antioxidation study. Fabrication of multifunctional nanoplatforms with quercetin is limited. In the present study, water-soluble quercetin derived nanoparticles (QFNPs) were fabricated through the one pot synthesis strategy with Fe3+, quercetin and poly (vinyl pyrrolidone) (PVP). The raw materials were dissolved in absolute ethanol and the mixed together. After stirring at room temperature for 6 h, the QFNPs could be simply harvested by centrifugation without the need of time-consuming dialysis procedure. Due to the protective effect of PVP, the synthesized nanoparticles could be well dispersed in water with the hydrodynamic size about 23 nm. DPPH free radical scavenging capacity assay showed QFNPs could act as efficient antioxidant. Besides antioxidation activity, the QFNPs also exhibited good photothermal capacity. Temperature stability result suggested the good stability of QFNPs between 35 and 95 °C. MTT and hemolysis assay showed the good biocompatibility of QFNPs. What's more, the QFNPs showed good cellular antioxidation activity and efficient photothermal killing effect to cancer cells (4T1 cells). The QFNPs could be promising nanoplatform for biomedical application.


Subject(s)
Antioxidants/pharmacology , Drug Carriers , Epithelial Cells/drug effects , Multifunctional Nanoparticles/chemistry , Povidone/chemistry , Quercetin/pharmacology , Animals , Antioxidants/chemistry , Antioxidants/radiation effects , Biphenyl Compounds/antagonists & inhibitors , Biphenyl Compounds/chemistry , Cell Line, Tumor , Epithelial Cells/pathology , Epithelial Cells/radiation effects , Female , Hot Temperature , Hyperthermia, Induced/methods , Light , Mammary Glands, Animal/pathology , Mice , Multifunctional Nanoparticles/radiation effects , Multifunctional Nanoparticles/ultrastructure , Particle Size , Picrates/antagonists & inhibitors , Picrates/chemistry , Quercetin/chemistry , Quercetin/radiation effects , Solubility , Water/chemistry
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