Polymer Composite Nanoparticles Research Articles

Multifunctional endogenous small molecule-derived polymer composite nanoparticles for the treatment of acute sepsis therapy

Multifunctional endogenous small molecule-derived polymer composite nanoparticles for the treatment of acute sepsis therapy

Conjugated Polymer Composite Nanoparticles Augmenting Photosynthesis-Based Light-Triggered Hydrogel Promotes Chronic Wound Healing.

Diabetic chronic wounds are characterized by local hypoxia, impaired angiogenesis, and bacterial infection. In situ, self-supply of dissolved oxygen combined with the elimination of bacteria is urgent and challenging for chronic nonhealing wound treatment. Herein, an oxygen-generating system named HA-L-NB/PFE@cp involving biological photosynthetic chloroplasts (cp)/conjugated polymer composite nanoparticles (PFE-1-NPs@cp) and light-triggered hyaluronic acid-based (HA-L-NB) hydrogel for promoting diabetic wound healing is introduced. Briefly, conjugated polymer nanoparticles (PFE-1-NPs) possess unique light harvesting ability, which accelerates the electron transport rates in photosystem II (PS II) by energy transfer, elevating photosynthesis beyond natural chloroplasts. The enhanced release of oxygen can greatly relieve hypoxia, promote cell migration, and favor antibacterial photodynamic therapy. Additionally, the injectable hydrogel precursors are employed as a carrier to deliver PFE-1-NPs@cp into the wound. Under light irradiation, they quickly form a gel by S-nitrosylation coupling reaction and in situ anchor on tissues through amine-aldehyde condensation. Both in vitro and in vivo assays demonstrate that the oxygen-generating system can simultaneously relieve wound hypoxia, eliminate bacteria, and promote cell migration, leading to the acceleration of wound healing. This study provides a facile approach to develop an enhanced oxygen self-sufficient system for promoting hypoxic tissue, especially diabetic wound healing.

Polymer composite microspheres loading 177Lu radionuclide for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer

BackgroundTransarterial radioembolization (TARE) with 90Y-labeled glass and resin microspheres is one of the primary treatment strategies for advanced-stage primary and metastatic hepatocellular carcinoma (HCC). However, difficulties of real-time monitoring post administration and embolic hypoxia influence treatment prognosis. In this study, we developed a new biodegradable polymer microsphere that can simultaneously load 177Lu and MgO nanoparticle, and evaluated the TARE therapeutic efficacy and biosafety of 177Lu-PDA-CS-MgO microspheres for HCC treatment.MethodsChitosan microspheres were synthesized through emulsification crosslink reaction and then conducted surface modification with polydopamine (PDA). The 177Lu and nano MgO were conjugated to microspheres using active chemical groups of PDA. The characteristics of radionuclide loading efficiency, biodegradability, blood compatibility, and anti-tumor effectwere evaluated both in vitro and in vivo. SPECT/CT imaging was performed to monitor bio-distribution and bio-stability of 177Lu-PDA-CS-MgO after TARE treatment. The survival duration of each rat was monitored. HE analysis, TUNEL analysis, immunohistochemical analysis, and western blot analysis were conducted to explore the anti-tumor effect and mechanism of composited microspheres. Body weight, liver function, blood routine examination were monitored at different time points to evaluate the bio-safety of microspheres.ResultsThe composite 177Lu-PDA-CS-MgO microsphere indicated satisfactory degradability, biocompatibility, radionuclide loading efficiency and radiochemical stability in vitro. Cellular evaluation showed that 177Lu-PDA-CS-MgO had significant anti-tumor effect and blocked tumor cell cycles in S phase. Surgical TARE treatment with 177Lu-PDA-CS-MgO significantly prolonged the medial survival time from 49 d to 105 d, and effectively inhibited primary tumor growth and small metastases spreading. Moreover, these microspheres indicated ideal in vivo stability and allowed real-time SPECT/CT monitoring for up to 8 weeks. Immunostaining and immunoblotting results also confirmed that 177Lu-PDA-CS-MgO had potential in suppressing tumor invasion and angiogenesis, and improved embolic hypoxia in HCC tissues. Further evaluations of body weight, blood test, and pathological analysis indicated good biosafety of 177Lu-PDA-CS-MgO microspheres in vivo.ConclusionOur study demonstrated that 177Lu-PDA-CS-MgO microsphere hold great potential as interventional brachytherapy candidate for HCC therapy.Graphical Polymer composite microspheres loading 177Lu radionuclide and MgO nanoparticles for interventional radioembolization therapy and real-time SPECT imaging of hepatic cancer.

Tuning Composition of Polymer and Porous Silicon Composite Nanoparticles for Early Endosome Escape of Anti-microRNA Peptide Nucleic Acids.

Porous silicon nanoparticles (PSNPs) offer tunable pore structure and easily modified surface chemistry, enabling high loading capacity for drugs with diverse chemicophysical properties. While PSNPs are also cytocompatible and degradable, PSNP integration into composite structures can be a useful approach to enhance carrier colloidal stability, drug-cargo loading stability, and endosome escape. Here, we explored PSNP polymer composites formed by coating of oxidized PSNPs with a series of poly[ethylene glycol-block-(dimethylaminoethyl methacrylate-co-butyl methacrylate)] (PEG-DB) diblock copolymers with varied molar ratios of dimethylaminoethyl methacrylate (D) and butyl methacrylate (B) in the random copolymer block. We screened and developed PSNP composites specifically toward intracellular delivery of microRNA inhibitory peptide nucleic acids (PNA). While a copolymer with 50 mol % B (50B) is optimal for early endosome escape in free polymer form, its pH switch was suppressed when it was formed into 50B polymer-coated PSNP composites (50BCs). We demonstrate that a lower mol % B (30BC) is the ideal PEG-DB composition for PSNP/PEG-DB nanocomposites based on having both the highest endosome disruption potential and miR-122 inhibitory activity. At a 1 mM PNA dose, 30BCs facilitated more potent inhibition of miR-122 in comparison to 40BC (p = 0.0095), 50BC (p < 0.0001), or an anti-miR-122 oligonucleotide delivered with the commercial transfection reagent Fugene 6. Using a live cell galectin 8-based endosome disruption reporter, 30BCs had greater endosomal escape than 40BCs and 50BCs within 2 h after treatment, suggesting that rapid endosome escape correlates with higher intracellular bioactivity. This study provides new insight on the polymer structure-dependent effects on stability, endosome escape, and cargo intracellular bioavailability for endosomolytic polymer-coated PSNPs.

Multifunctional metal-free rechargeable polymer composite nanoparticles boosted by CO2

Herein, we present a multigram scale-up route for the preparation of novel polymer composite nanoparticles as potential multifunctional rechargeable material for future, sustainable batteries. The nanoparticles (20 nm) comprise three innocuous yet functional interpenetrated macromolecular networks: polypyrrole, methylcellulose, and lignin. They are uniquely assembled in strands or chains (∼200 nm) such as necklace beads and show long-term stability as water dispersion. We find that an aqueous suspension of this hierarchical nanomaterial shows two sets of reversible redox peaks, separated by ∼600 mV, originating from the catechol moieties present in the lignin biopolymer. Remarkably, the addition of carbon dioxide increased the capacity of one of the redox processes by 500%. Importantly, the three redox stages occur in the presence of the same nanostructured polymer so being a potentially bifunctional material to be used in advanced electrochemical systems. The new properties are attributed to an intrinsic chemical and electronic coupling at the nanoscale among the different building blocks of the metal-free polymer composite and the structural rearrangement of the interpenetrated polymer network by the incorporation of CO2. We have provided both a new electrochemically multifunctional hierarchically structured material and a facile route that could lead to novel sustainable energy applications.

Garlic oil–loaded PLGA nanoparticles with controllable size and shape and enhanced antibacterial activities

ABSTRACTThe present work focuses on producing polymer composite nanoparticles (NPs) composed of garlic oil (GO) and poly(lactic‐co‐glycolic) acid (PLGA) by the single emulsion/solvent evaporation (SE/SE) method and high‐speed homogenizing. Different preparation parameters were found to greatly affect the stability and size uniformity of the prepared PLGA/GO NP formulations, which were carefully controlled. Scanning electron microscopy, Fourier transform infrared spectroscopy, and UV–vis spectroscopy and dynamic light scattering and zeta potential were used to characterize the NPs. Antibacterial assessment of the prepared PLGA/GO NPs against E. coli and S. aureus was carried out. Interestingly, the NP size ranged between 201 and 319 nm, which is 10 times less than the size of the regular GO particles in bulk solution. The antibacterial activities show enhancement by 70–78% of bacterial inhibition compared with a GO bulk solution. This work sheds light on the potential use of GO NP formulations as nanobiotics and the critical NP preparation parameters that need to be considered. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46133.

Generating Bulk-Scale Ordered Optical Materials Using Shear-Assembly in Viscoelastic Media

We review recent advances in the generation of photonics materials over large areas and volumes, using the paradigm of shear-induced ordering of composite polymer nanoparticles. The hard-core/soft-shell design of these particles produces quasi-solid “gum-like” media, with a viscoelastic ensemble response to applied shear, in marked contrast to the behavior seen in colloidal and granular systems. Applying an oscillatory shearing method to sub-micron spherical nanoparticles gives elastomeric photonic crystals (or “polymer opals”) with intense tunable structural color. The further engineering of this shear-ordering using a controllable “roll-to-roll” process known as Bending Induced Oscillatory Shear (BIOS), together with the interchangeable nature of the base composite particles, opens potentially transformative possibilities for mass manufacture of nano-ordered materials, including advances in optical materials, photonics, and metamaterials/plasmonics.

Multi-lobed composite polymer nanoparticles prepared by conventional emulsion polymerization

The vast majority of latex particles, including those made from multiple polymers, are spherical in shape. This is a result of the minimization of the combined interfacial free energies at the polymer particle–water interface and the polymer–polymer interfaces within the particle. Yet there are special situations in which latex particles containing two, incompatible polymer phases can form asymmetric, multi-lobed particles during conventional, two stage emulsion polymerizations. Here we report on a variety of situations used to produce these interesting polymer particles and discuss the mechanism by which they are formed. The key condition is that the reaction process be carried out in a manner in which the second stage oligoradicals in the water are not allowed to significantly penetrate the first stage latex particle during the reaction. Then, the important variables are the relative differences between the interfacial tensions at the water-polymer interface for the two polymers in question, and the second stage polymer chain diffusivity on the surface of the first stage particles. By extension, the same fundamental parameters of interfacial tensions and polymer chain surface diffusion apply to the morphology possibilities when inorganic first stage particles are used to create inorganic-organic composite latices.

Heterogeneous polymer composite nanoparticles loaded in situ gel for controlled release intra-vaginal therapy of genital herpes

Herpes simplex virus causes serious and contagious genital infections in high percentage of female population world-wide. Acyclovir is a clinically successful antiviral molecule till date, in-spite of limitations as poor solubility, low half-life, reduced oral bioavailability and side effects at higher doses. In the present work, controlled release in situ gelling system loaded with polymeric nanoparticles of acyclovir containing a dose of drug equivalent to 105mg/day has been developed. The formulation containing drug loaded polyvinyl pyrrolidone⿿Eudragit RSPO hybrid polymeric nanoparticles (Size ⿼99±3nm, Zeta ⿼+26.1±1.5mV) in 15% Pluronic F-127 gel exhibited improved permeability through vaginal membrane (KP=2.20±0.19ÿ10⿿6cm/s). The nanoparticles showed enhanced viability for vaginal epithelial cell lines up to concentration of 100⿿250μg/mL. The formulation was evaluated for bioavailability and biodistribution through intra-vaginal administration in rat models. The nanoparticle in situ gel formulation maintained an average therapeutic drug level of 0.6±0.2μg/mL in plasma for 24h. Significant improvement in mean residence time of the drug (12.52±1.12h) was observed with a two-fold increase in the relative bioavailability (AUC0⿿24h=14.92±2.44μgh/mL) compared to that of the pure drug (7.18±1.79μgh/mL). The tissue distribution was 2⿿3 folds higher in animals treated with nanoparticles in situ gel compared to that of pure drug. Sustained release of drug in vivo was demonstrated, ensuring the suitability of the formulation for clinical therapy in female population.

Ratiometric Nanothermometer Based on Rhodamine Dye-Incorporated F127-Melamine-Formaldehyde Polymer Nanoparticle: Preparation, Characterization, Wide-Range Temperature Sensing, and Precise Intracellular Thermometry.

A series of fluorescent nanothermometers (FTs) was prepared with Rhodamine dye-incorporated Pluronic F-127-melamine-formaldehyde composite polymer nanoparticles (R-F127-MF NPs). The highly soluble Rhodamine dye molecules were bound with Pluronic F127 micelles and subsequently incorporated in the cross-linked MF resin NPs during high-temperature cross-link treatment. The morphology and chemical structure of R-F127-MF NPs were characterized with dynamic light scattering, electron microscopy, and Fourier-transform infrared (FTIR) spectra. Fluorescence properties and thermoresponsivities were analyzed using fluorescence spectra. R-F127-MF NPs are found to be monodispersed, presenting a size range of 88-105 nm, and have bright fluorescence and high stability in severe treatments such as autoclave sterilization and lyophilization. By simultaneously incorporating Rhodamine B and Rhodamine 110 (as reference) dyes at a doping ratio of 1:400 in the NPs, ratiometric FTs with a high sensibility of 7.6%·°C(-1) and a wide temperature sensing range from -20 to 110 °C were obtained. The FTs exhibit good stability in solutions with varied pH, ionic strengths, and viscosities and have similar working curves in both intracellular and extracellular environments. Cellular temperature variations in Hela cells during microwave exposure were successfully monitored using the FTs, indicating their considerable potential applications in the biomedical field.

Micro-flow assisted synthesis of fluorescent polymer nanoparticles with tuned size and surface properties

AbstractNumerous different photonics and biomedical applications depend on the fluorescent polymer micro- and nanoparticles. Besides optical or spectroscopic properties, the performance of the polymer nanoparticles is determined by their size, size distribution, and surface charge. Moreover, in order to realize a very uniform performance, the functional polymer nanoparticles should be of high homogeneity and demand for the preparation in a minimum number of synthesis steps. Here, we present a microfluidic-assisted synthesis of different types of reproducible fluorescent polymer nanoparticles with tuned size (40 nm up to 600 nm) and surface charge (ζ potential=-52 mV up to +45 mV). Four different preparation strategies were introduced for fluorophore-functionalized nanoparticles: (a) noncovalent binding of fluorophores with high loading, (b) covalent linking of fluorophores with enhanced stability, (c) surface-anchored fluorophores by hydrophobic interactions for triple function at the same time, and (d) surface immobilization of biomolecules and fluorophore by ionic as well as secondary interactions. In this way, four different classes of nanoparticles suited for different applications were prepared with a spherical shape as a model system. Moreover, the principle has been extended to the different types of nonspherical and composite polymer nanoparticles.

Carboxylated Magnetite Composite Polymer Nanoparticles with Mosaic Structure for Biomedical Application

In this article, a microemulsion method for preparation of magnetite composite polymer nanoparticles of Fe3O4@poly(styrene-methacrylic acid) (MNP@PSMA) crosslinked with1,6-hexanediol diacrylate (HDD) insitu with carboxyl functionality on the surface has been reported. Structure and morphology of the nanoparticles was studied by Fourier Transform Infrared spctroscopy (FTIR), X ray Diffraction (XRD), Thermal Gravimetric Analyser (TGA), Vibrating Sample Magnetometer (VSM) and Transmission Electron Microscopy (TEM). VSM studies confirmed saturation magnetization of 20.0 emu/g in an external magnetic field. Nanoparticles formed were of 30 nm in diameter with narrow size distribution and mosaic structure providing a large surface area useful for application in bioseparation. Experimental results of covalent coupling of composite nanoparticles indicated maximum protein binding capacity of 350 mg bovine serum albumin (BSA) per gram.

Surface Molecular Imprinting on Manganese-Doped Zinc Sulfide Quantum Dots for Fluorescence Detection of Bisphenol A in Water

Manganese-doped zinc sulfide quantum dot based molecularly imprinted polymer composite nanoparticles were prepared. Bisphenol A served as the template and 3-aminopropyltriethoxysilane and tetraethoxysilicane were the functional monomer and cross-linker, respectively. The quantum dots exhibited excellent selectivity, fast adsorption kinetics, high stability, and good dispersion in aqueous media. The quenched fluorescence emission was proportional to the concentration of Bisphenol A without any preconcentration. This highly selective fluorescence sensor had a linear response from 10 to 700 nanograms per milliliter with a correlation coefficient of 0.9860. The relative standard deviation of five replicate measurements of 100 nanograms per milliliter Bisphenol A was 2.2 percent. The recovery of fortified Bisphenol A in water samples ranged from 98.70 to 105.50 percent.

Conjugated polymer composite nanoparticles by rapid mixing.

Composite nanoparticles from poly[(9,9-di-n-octylfluoren-2,7-diyl)-alt-(benzo[2,1,3]thiadiazol-4,8-diyl)] (F8BT) and poly(9,9-di-n-hexylfluoren-2,7-diyl) (PF) with embedded inorganic nanoparticles (TiO2 , CdSe, and CdSe/CdS) are prepared through kinetic trapping by rapid turbulent mixing in a multi-inlet vortex mixer without the need for polymer functionalization. High contents of inorganic materials up to 50-60 wt% are realized for all composites. The influence of flow ratios, sodium dodecyl sulfate (SDS) concentration, and absolute flow rates on the particle size and morphology is studied. High water-to-THF ratios and high total flow rates around 2 m s(-1) yield particle sizes below 50 nm. By adjusting these parameters, controlled particle sizes between 30 to several hundred nanometers are obtained. Composite particles from CdSe/CdS and F8BT or PF show a strong quenching of the polymer emission and near exclusive emission from the inorganic nanocrystal, which indicates an efficient energy transfer with fluorescence quantum yields of 23% for the F8BT/CdSe/CdS composites and 21% for the PF/CdSe/CdS composites. The dispersions are colloidally stable for several months.

A Facile Method to Synthesize Responsive Magnetic Polymer Composite Nanoparticles with Multifunctional Groups

Magnetite nanoparticles (MNPs) coated with poly (divinylbenzene-co-glycidyl methacrylate) particles (mPDGs) are prepared by co-polymerization of 1,4-divinylbenzene and glycidyl methacrylate monomers via batch emulsion polymerization. The Fe3O4nanoparticles modified by oleic acid are obtained by chemical precipitation. The chemical composition, morphology, magnetic content, magnetic properties and particle size of the composite particles are investigated using transmission electron microscopy, thermogravimetric analysis, vibrating sample magnetometer, and dynamic light scattering, respectively. The results show that the magnetic nanoparticles have been coated by 1,4-divinylbenzene and glycidyl methacrylate, with the high saturation magnetization being 33.66 emu/g. The mean size of the mPDGs with good dispersion is about 200 nm. Subsequently, the polymer shell with reactive epoxy group is expected to be useful for chemical grafting of any biomolecule containing reactive functional groups (-NH2, -OH, -COOH, etc) or can be chemically modified to desired functional groups. These magnetic nanospheres with multifunctional groups have potential application in biomedical applications.

Hyaluronidase enzyme core-5-fluorouracil-loaded chitosan-PEG-gelatin polymer nanocomposites as targeted and controlled drug delivery vehicles

This study examines the performance of novel hyaluronidase enzyme core-5-fluorouracil-loaded chitosan-polyethylene glycol-gelatin polymer nanocomposites, which were prepared using an ionic gelation technique, as targeted and controlled drug delivery vehicles. These hyaluronidase-loaded nanoparticles have recently been proposed as targeted and controlled drug delivery vehicle systems to tissues due to their ability to loosen the intercellular connective matrix of hyaluronic acid. The encapsulation efficiency and loading capacities of the nanoparticles demonstrated that these nanocomposites displayed sufficient binding ability, which depends on the pH and initial concentration of the drug. The cytotoxic effects of the chitosan-hyaluronidase-5-fluorouracil (CS-HYL-5-FU), chitosan-hyaluronidase-5-fluorouracil polyethylene glycol (CS-HYL-5-FU-PEG), and chitosan-hyaluronidase-5-fluorouracil polyethylene glycol-gelatin (CS-HYL-5-FU-PEG-G) nanoparticles were assessed using MTT assays, and the nanovectors were found to be less cytotoxic than the chemotherapeutic 5-FU after incubation for 3-12h. The particle sizes of the CS-HYL-5-FU, CS-HYL-5-FU-PEG and CS-HYL-5-FU-PEG-G polymer composites were between 300 and 580 nm, as determined by a Zetasizer. Scanning electron microscopy (SEM) analysis indicated that the nanocomposites exhibit a clear, smooth surface and fine morphology. Linkages of the polymers, enzyme, and drug were confirmed by FTIR spectroscopy. Atomic fluorescence microscopy (AFM) analysis confirmed the size of the polymer composite nanoparticles. Therefore, this work established that the drug can be successfully encapsulated in chitosan-polyethylene glycol-gelatin-accompanied hyaluronidase nanoparticles with a homogeneous distribution. These nanoparticles can be potential carriers for targeted and controlled drug delivery to cancer cells.

Gold nanoparticle-enhanced luminescence of silicon quantum dots co-encapsulated in polymer nanoparticles

The preparation of two-component polymer composite nanoparticles encapsulating both Si quantum dots (SiQDs) and Au nanoparticles (AuNPs) by a single step miniemulsion polymerization of divinylbenzene is described. This simple and robust method affords well-defined polymer composite nanoparticles with mean diameters in a range of 100-200 nm and with narrow polydispersity indices as determined by dynamic light scattering and transmission electron microscopy. The successful encapsulation of AuNPs within poly(divinylbenzene) was confirmed by UV-visible spectroscopy and from TEM images. Plasmon-enhanced fluorescence of the luminescence of the SiQDs by AuNPs encapsulated within the polymer composite nanoparticles was evaluated by confocal microspectroscopy, and luminescence enhancements of up to 15 times were observed. These observations indicate that the luminescence of the SiQDs is enhanced by the proximity of the AuNPs. The polymer composite nanoparticles were successfully ink-jet printed onto a glass substrate, which demonstrates that these composites are processable in printing applications.

Synthesis of Magnetite/Amphiphilic Polymer Composite Nanoparticles as Potential Theragnostic Agents

This study describes the synthesis of magnetite/amphiphilic polymer composite nanoparticles that can be potentially used simultaneously for cancer diagnosis and therapy. The synthesis method was a one-shot process wherein magnetite nanoparticles were mixed with core-crosslinked amphiphilic polymer (CCAP) nanoparticles, prepared using a copolymer of a urethane acrylate nonionomer (UAN) and a urethane acrylate anionomer (UAA). The CCAP nanoparticles had a hydrophobic core and a hydrophilic exterior with both PEG segments and carboxylic acid groups, wherein the magnetite nanoparticles were coordinated and stabilized. According to DLS data, the ratio of UAN to UAA and the ratio of magnetite to polymer are keys to controlling the size and thus, the stability of the composite nanoparticles. The magnetic measurement indicated that the composite nanoparticles had superparamagnetic properties and high saturation magnetization. The preliminary magnetic resonance imaging showed that the particles produced an enhanced image even when their concentration was as low as 80 microg/ml.

Fabrication and characterization of thermo-sensitive magnetic polymer composite nanoparticles

Novel dual-functional nanospheres composed of Fe3O4 nanoparticles embedded in a thermo-sensitive polymer were synthesized by emulsifier-free emulsion polymerization. The Fe3O4 nanoparticles were prepared by chemical precipitation. The surface of these particles was modified by oleic acid to achieve stability against agglomeration. These stable particles were then polymerized using N-isopropylacrylamide as the main monomer, divinylbenzene as the crosslinker and potassium persulfate as the initiator. The nanospheres were characterized by Fourier-transform infrared spectrum, transmission electron microscopy, thermogravimetric analysis, vibrating sample magnetometer and dynamic light scattering. The results show that the lower critical solution temperature of thermo-sensitive magnetic immunomicrospheres was between 40 and 45°C.

Effect of iron nanoparticles in the films of composite materials and carbon nanotubes on the angular dependence of X-ray emission

The angular dependences of X-ray emission were measured for a series of polymer film samples with different concentration of finely dispersed iron. X-ray fluorescence maximum was found to shift toward higher angles with increasing the iron concentration in a sample. The form of angular dependences of X-ray emission was calculated taking into account the particle absorption coefficients in a composite material for incident and emitted radiation. The experimental and theoretical dependences were compared to estimate the content of nanoparticles in the polymer composite and iron nanoparticles in the samples of oriented carbon nanotubes.