Functionalized Polymer Nanoparticles Research Articles

Self-stabilized precipitation polymerization: principle, method and application

A novel heterogeneous polymerization technique, termed as self-stabilized precipitation (2SP) polymerization, was developed beyond emulsion/dispersion/suspension. Through quiescent polymerization, self-nucleation and surface deposition process, a stable colloid composed of uniform polymer particles and reaction medium was formed without the use of any stabilizers. More importantly, the polymer particles can be easily separated from the solvent and the supernatant liquid can be recycled, making this strategy a truly “green” polymerization process. This technique leads to several revolutionary advances: (1) one of the most simple, efficient and green strategies to produce uniform, size-tunable and functional polymer nanoparticles; (2) the polymerization reactivity of α-olefin is highly enhanced through copolymerization with maleic anhydride; (3) generation of functional copolymer particles directly from single olefinic monomer or complex olefinic mixtures (including C4/C5/C9 fractions) without any further purification, which provides a new way to transform huge amount of olefinic compounds in C4/C5/C9 fractions into valuable functional polymers.

In situ polymerization and polymer grafting to stabilize polymer-functionalized nanoparticles in polymer matrices

Control of nanoparticle dispersion within a polymer matrix is a critical consideration when designing solid state hybrid polymer/inorganic nanoparticle materials. Polymer-functionalized nanoparticles are effective hybrid components for increasing particle miscibility in polymer matrices. Entropic and enthalpic contributions to the dispersion state of polymer-functionalized nanoparticles are well-understood and have been used extensively to enhance nanoparticle miscibility in polymer matrices. However, systems of immiscible graft and matrix chains remain understudied, in part due to the challenges associated with mixing unlike components. Here, a new method for stabilizing polymer-functionalized nanoparticles in an immiscible matrix is reported. Poly(cyclooctadiene) (PCOD) functionalized nanoparticles are dispersed within poly(styrene) and poly(methyl methacrylate) matrices by an in situ polymerization and polymer grafting process in which polymer-grafted nanoparticles are initially well-solubilized in a monomer solution prior to monomer polymerization. The in situ polymerization arrests particle mobility as the matrix increases in chain length, and thermodynamic penalties to mixing are reduced by the in situ grafting of matrix chains from the PCOD segments on the nanoparticle surfaces. This method adapts commercially relevant free-radical polymerization processes for the development of well-dispersed hybrid polymer/inorganic nanoparticle materials. The reported method is a potential avenue to improve particle dispersion needed for solid state material reinforcement without relying on miscible particle and polymer components.

Polymer-functionalized polymer nanoparticles and their behaviour in suspensions

In concentrated suspensions of polymer-functionalized nanoparticles, the softness of the core nanoparticles has a crucial effect on the mechanical behaviour of the resulting colloidal gels.

Entropic Effects in Solvent-Free Bidisperse Polymer Brushes Investigated Using Density Functional Theories.

Solvent-free polymer-functionalized nanoparticles form a special type of colloid composed of inorganic cores self-suspended by their grafted coronas. In the absence of intervening solvent molecules, the fluidity of the system is provided by these tethered polymers as they fill the space. Here, we study the structure and interaction of neighboring polymer-grafted surfaces in the solvent-free condition using mean-field density functional theories. For opposing flat surfaces, the brush configuration and the associated energy landscape are semianalytically investigated given the incompressibility of the tethered entropic chains. The effect of brush polydispersity (including variations in both chain length and surface grafting density) is considered by two bidisperse models corresponding to different physical scenarios: one for opposing brushes uniformly mixed with two species at a fixed grafting density, and the other for opposing brushes with distinct chain lengths and grafting densities. The space-filling capabilities of the neighboring coronas differ not only by their ratio of radii of gyration for the composing polymers but also by their ratio of grafting densities. We show that the system energy depicts a steric repulsion as the brushes are compressed, which is typical for hairy particles in a solvent. However, as the interwall separation increases, the cooperative stretching of the chains leads to an entropic attraction between them, a unique characteristic of solventless systems. The corresponding brush profiles change from a bell-like shape to a more step-function-like feature as the interwall spacing increases significantly. The interwall separation associated with the overall free energy minimum therefore characterizes the favorable interparticle spacing for solvent-free polymer-functionalized particles. The limiting accessible parameter space of polymer sizes and grafting densities subjected to the space-filling constraint is comprehensively explored for representative interparticle spacing characterizing the compressed, relaxed, and stretched regimes for a given polymer species, respectively. Such information would be useful for guiding the design of experimental solvent-free polymer-functionalized nanoparticles.

Fluorescent Nanoparticles Synthesized by Carbon-Nitride-Stabilized Pickering Emulsion Polymerization for Targeted Cancer Cell Imaging.

Graphitic carbon nitride (CN) has been found to possess amphiphilic properties, enabling it to act as a solid emulsifier to stabilize the Pickering emulsion and subsequent polymerization. Herein, we used CN-stabilized Pickering emulsion polymerization to prepare molecularly imprinted polymer nanoparticles, which showed selective binding toward cancer cells. Taking advantage of its intrinsic amphiphilicity and emission properties, CN served as both the emulsifier in the polymerization process and emissive probe for cellular imaging application. Sialic acid (SA), as an important indicator of some certain cancers, was introduced into the polymer nanoparticles by forming reversible bonds with 4-vinylphenylboronic acid comonomer and removed by adjusting the pH value. The obtained SA-imprinted polymer nanoparticles exhibited good biocompatibility and excellent targeted imaging of DU 145 cells, which are prostate cancer cells having an SA-overexpressed surface. This work provides an easy, low-cost, low-toxicity, and large-scale strategy to prepare various functional polymer nanoparticles.

Nano Spray‐Dried Block Copolymer Nanoparticles and Their Transformation into Hybrid and Inorganic Nanoparticles

AbstractA novel combination of block copolymer (BCP) nano spray‐drying (NSD), solvent annealing, and selective metal oxide growth is utilized to create functional polymer nanoparticles, polymer‐metal‐oxide hybrid nanoparticles, and templated metal oxide nanoparticles with tunable composition, internal morphology, and porosity. NSD of BCPs from chloroform and toluene solutions results in porous and nonporous nanoparticles, respectively, with various degrees of phase separation. Further tuning of the nanoparticle internal morphology is performed by solvent annealing the spray‐dried particles with judicious choice of the nonsolvent dispersion medium and the surfactant, yielding assembly of both blocks at the surface of the nanoparticles. Finally, ZnO and Al2O3 are grown inside the polar blocks of phase‐ordered nanoparticles using a sequential infiltration synthesis method, in a post‐assembly process, resulting in hybrid BCP‐ZnO particles and BCP‐templated Al2O3 nanoparticles, as demonstrated by scanning transmission electron microscopy tomography. These structure engineering methods open new ways to direct and template functional nanoparticles.

Indocyanine green/doxorubicin-encapsulated functionalized nanoparticles for effective combination therapy against human MDR breast cancer.

To overcome low therapeutic efficacy of chemotherapy against multidrug resistance (MDR) breast cancer, a combination therapy system based upon functionalized polymer nanoparticles comprising poly(γ-glutamic acid)-g-poly(lactic-co-glycolic acid) (γ-PGA-g-PLGA) as the major component was developed. The NPs were loaded with doxorubicin (DOX) and indocyanine green (ICG) for dual modality cancer treatment and coated with cholesterol-PEG (C-PEG) for MDR abrogation in treatment of human MDR breast cancer. The in vitro cellular uptake of the DOX/ICG loaded nanoparticles (DI-NPs) by MDR cancer cells was significantly enhanced owing to effective inhibition of the P-gp activity by C-PEG and γ-PGA receptor-mediated endocytosis. DOX localization in cytoplasm and nucleus was observed particularly with the photo-thermal effect that facilitated intracellular drug release. As a result, the C-PEG coated DI-NPs after photo-irradiation exhibited a synergistic effect of combination (chemo/thermal) therapy to depress the proliferation of MDR cancer calls. The ex vivo biodistribution study revealed an enhanced tumor accumulation of C-PEG (2000) coated DI-NPs in MCF-7/MDR tumor-bearing nude mice due to the excellent EPR effects by the NP surface PEGylation. The MDR tumor growth was almost entirely inhibited in the group receiving combination therapy from CP2k-DI-NPs and photo-irradiation along with substantial cell apoptosis of tumor tissues examined by immunohistochemical staining. The results demonstrate a promising dual modality therapy system, CP2k-DI-NPs, developed in this work for effective combination therapy of human MDR breast cancer.

Tailored functionalized polymer nanoparticles using gamma radiation for selected adsorption of barium and strontium in oilfield wastewater

To improve oil recovery from oilfield wells mineral scales derived by insoluble BaSO4 and SrSO4 salts during oil extraction should be diminished. In this work, adsorption selectivity of Barium (Ba2+) and Strontium (Sr2+) ions associated with saline formation waters was examined for the first time using nano-sized bi-functional polymer blend synthesized by Cobalt-60 (60Co) γ-rays, as green technology. A bifunctional polymer formed from poly(acrylonitrile)/(styrene-butadiene rubber) homogenous blend is functionalized by -SO3H and -COOH terminal groups (termed as SASB). Those functional groups were selected based on systematic calcium (Ca2+) ions adsorption studies of carboxylate containing molecules. Main and binary interactive effects of solution pH (3–9), adsorbents dose (1-3 g/L), total dissolved salts (TDS, up to 30 g/L), initial Ba2+ and Sr2+ concentrations (10-500 mg/L) and temperature (20–50 oC) on the adsorption selectivity were examined and optimized using Plackett-Burman factorial design (PBD) combined with multiple regression analysis. The regression statistics revealed the significance of quadratic polynomial model to optimize interactive sorption conditions from salty waters with high accuracy level (R2≈ 0.99) rather than linear and two-way interactive models at 95% confidence level. Interestingly finding, the regression and experimental data proved that the presence of up to 10 g/L TDS from alkali metal ions had a significant effect on the enhancement sorption capacity of Ba2+ and Sr2+ when using the prepared sorbent. The SASB adsorbent showed higher sorption selectivity with maximum equilibrium capacity (qmg/g) of 175.3 mg Ba+2 and 210.5 mg Sr+2 per each gram sorbent used in kinetic study. Adsorption kinetics of Ba2+ and Sr2+ sorption by both adsorbents obey pseudo-first and pseudo-second order kinetics, respectively. In sum, the adsorptive power of SASB sorbent is found to be in reverse order of the electronegativity and the hydration radii of the metal ions.

Functional Polymer Nanocarriers for Photodynamic Therapy.

Photodynamic therapy (PDT) is an appealing therapeutic modality in management of some solid tumors and other diseases for its minimal invasion and non-systemic toxicity. However, the hydrophobicity and non-selectivity of the photosensitizers, inherent serious hypoxia of tumor tissues and limited penetration depth of light restrict PDT further applications in clinic. Functional polymer nanoparticles can be used as a nanocarrier for accurate PDT. Here, we elucidate the mechanism and application of PDT in cancer treatments, and then review some strategies to administer the biodistribution and activation of photosensitizers (PSs) to ameliorate or utilize the tumor hypoxic microenvironment to enhance the photodynamic therapy effect.

Visible light-, pH-, and cyclodextrin-responsive azobenzene functionalized polymeric nanoparticles

Multiple stimuli-responsive nanoparticles that could respond to visible-light, pH and host-guest interactions were fabricated by self-assembly of tetra-ortho-methoxy-substituted azobenzene (mAzo) functionalized poly(dimethylaminoethyl methacrylate) (PDMAEMA) (PDMAEMA-mAzo), which was synthesized by quaternization between the azobenzene derivative (mAzo-Br) and the dimethylaminoethyl units of PDMAEMA. The amphiphilic azobenzene-functionalized polymer (PDMAEMA-mAzo) would self-assemble into a micellar nanoparticle consisting of hydrophobic mAzo groups as a core and hydrophilic PDMAEMA segments as a shell. Under green light irradiation, the azobenzene could isomerize from the trans form to the cis, while the morphology of the nanoparticle changed little and the loaded Nile red would not be released. At acidic condition, the azobenzene mAzo and PDMAEMA could be protonated and the nanoparticle was swollen and the loaded Nile red would be released. When mixed with cyclodextrin (CD), the nanoparticles were dissociated due to the formation of the host-guest complex of CD and azobenzene. Upon green light irradiation, the trans azobenzene changed to the cis form and the host-guest interaction could be disrupted, where the cis-azobenzene-containing polymer would self-assemble into nanoparticles. The dissociation of the nanoparticles upon addition of CD would induce the release of loaded Nile red. The prepared multiple-responsive azobenzene functionalized polymer nanoparticles may offer significant opportunities for diverse applications in the fields of nanotechnology and biotechnology for controlled release as smart nanocarriers.

New Insights into RAFT Dispersion Polymerization-Induced Self-Assembly: From Monomer Library, Morphological Control, and Stability to Driving Forces.

Polymerization-induced self-assembly (PISA) has been established as an efficient, robust, and versatile approach to synthesize various block copolymer nano-objects with controlled morphologies, tunable dimensions, and diverse functions. The relatively high concentration and potential scalability makes it a promising technique for industrial production and practical applications of functional polymeric nanoparticles. This feature article outlines recent advances in PISA via reversible addition-fragmentation chain transfer dispersion polymerization. Considerable efforts to understand morphological control, broaden the monomer library, enhance morphological stability, and incorporate multiple driving forces in PISA syntheses are summarized herein. Finally, perspectives on the future of PISA research are discussed.

Intrinsically fluorescent and highly functionalized polymer nanoparticles as probes for the detection of zinc and pyrophosphate ions in rabbit serum samples

Intrinsically fluorescent polymer nanoparticles (F-PNPs) were synthetized from 2-hydroxy-5-methylisophthalaldehyde and melamine by solvothermal method. F-PNPs can emit strong yellow green fluorescence at 542 nm without the conjugation to any external fluorescent agent and surface modification. Owing to the abundant amino and hydroxyl groups on their surface, the F-PNPs possess multiple binding sites, good biocompatibility and excellent water-solubility. Addition of Zn2+ to the F-PNPs solution resulted in a blue shift (Δλ=40 nm) with obvious enhancement in the fluorescence intensity at 502 nm; while there was negligible change in the presence of other metal ions. The subsequent treatment with pyrophosphate (PPi) can cause fluorescence recovery of F-PNPs by pulling the Zn2+ out of the coordination cavity of F-PNPs-Zn2+ nanocomposites. No interference was observed from other anions and nucleotides, making the F-PNPs-Zn2+ ensembles highly sensitive and selective nanoprobes for PPi. The detection limit is 2.75 × 10−8 M/L and 7.63 × 10−8 M/L for Zn2+ and PPi, respectively. The proposed nanoprobes were then used for detecting the recovery of Zn2+ and PPi in rabbit serum samples, which were found to be 99.4–104.2% and 98.6–104.7%, respectively. The present strategy for the fabrication of nanoparticles may offer a new sight for the preparation of polymer nanostructures. The F-FNPs based probes can provide an accurate method for the detection of Zn2+ and PPi in serum samples.

Modular Adjustment of Swelling Behaviors of Surface-Modified Solvent-Responsive Polymeric Nanoparticles Based on Cellulose 10-Undecenoyl Ester

Functional polymeric nanoparticles (NPs) have attracted intense interest because of their broad applications. However, most of them focused on characteristics, behaviors, properties, or functionalities of the NPs, while neglecting the interaction between NPs and solvents and thus the influence of solvents on the physical–chemical properties of NPs. In this paper, NPs based on cellulose 10-undecenoyl ester with total substitution of hydroxyl groups by undecenoyl moieties were prepared in various organic dispersants via nanoprecipitation. These NPs were further surface-modified with diverse functionalities via thiol–ene reactions on the terminal vinyl groups of undecenoyl moieties. The swelling behaviors of the resultant surface-modified NPs were systematically investigated via adding corresponding swelling solvents to the dispersions, fitting the swelling modes to different types of functions, and analyzing the factors influencing the swelling processes. It is concluded that different interactions includin...

Polymer-functionalized nanoparticles for improving oil displacement

This work focuses on the synthesis, functionalization, and characterization of magnetic nanoparticles to be used for improving the oil recovery in the oil exploitation industry. In this manuscript we explore three different types of hydrophobic/hydrophilic functionalization through a silanized particle: with styrene, with acrylic acid and with a copolymer of styrene and maleic acid. Further application of such nanoparticles dispersions (nanofluid) are discussed as the wetting and spreading behaviour of liquids on the solid surfaces change if the wettability of solid surface is altered. In order to investigate the influence of wettability alternation on enhancing oil recovery after nanofluid treatment, flushing oil experiment and contact angle measurement were conducted in our laboratory. The results indicated that nanofluid can produce a better flushing efficiency compared with brine solution, and the contact angles of oil phase increased from 13° to 37° after nanofluid treatment (0.005% w/w). We focus on the synthesis of magnetic iron oxide nanoparticles considering recovering possibility.

Self-Stabilized Precipitation Polymerization and Its Application.

An effective, value-added use of the large amounts of olefinic compounds produced in the processing of petroleum, aside from ethylene and propylene, has been a long outstanding challenge. Here, we developed a novel heterogeneous polymerization method, beyond emulsion/dispersion/suspension, termed self-stabilized precipitation (2SP) polymerization, which involves the nucleation and growth of nanoparticles (NPs) of a well-defined size without the use of any stabilizers and multifunctional monomers (crosslinker). This technique leads to two revolutionary advances: (1) the generation of functional copolymer particles from single olefinic monomer or complex olefinic mixtures (including C4/C5/C9 fractions) in large quantities, which open a new way to transform huge amount of unused olefinic compounds in C4/C5/C9 fractions into valuable copolymers, and (2) the resultant polymeric NPs possess a self-limiting size and narrow size distribution, therefore being one of the most simple, efficient, and green strategies to produce uniform, size-tunable, and functional polymeric nanoparticles. More importantly, the separation of the NPs from the reaction medium is simple and the supernatant liquid can be reused; hence this new synthetic strategy has great potential for industrial production.

Self-Assembly and Surface Patterning of Polyferrocenylsilane-Functionalized Gold Nanoparticles.

Chemical and topographic surface patterning of inorganic polymer-functionalized nanoparticles (NPs) and their self-assembly in nanostructures with controllable architectures enable the design of new NP-based materials. Capping of NPs with inorganic polymer ligands, such as metallopolymers, can lead to new synergetic properties of individual NPs or their assemblies, and enhance NP processing in functional materials. Here, for gold NPs functionalized with polyferrocenylsilane, two distinct triggers are used to induce attraction between the polymer ligands and achieve NP self-assembly or topographic surface patterning of individual polymer-capped NPs. Control of polymer-solvent interactions is achieved by either changing the solvent composition or by the electrooxidation of polyferrocenylsilane ligands. These results expand the range of polymer ligands used for NP assembly and patterning, and can be used to explore new self-assembly modalities. The utilization of electrochemical polymer oxidation stimuli at easily accessible potentials broadens the range of stimuli leading to NP self-assembly and patterning.

Dynamics and Morphology of Nanoparticle-Linked Polymers Elucidated by Nuclear Magnetic Resonance.

Nanoparticles are frequently modified with polymer layers to control their physical and chemical properties, but little is understood about the morphology and dynamics of these polymer layers. We report here an NMR-based investigation of a model polymer-modified nanoparticle, using multiple NMR techniques including 1H NMR, diffusion-ordered spectroscopy (DOSY), total correlation spectroscopy (TOCSY), and T2 relaxometry to characterize the dynamics of the nanoparticle-polymer interface. Using 5 nm detonation nanodiamond covalently linked to poly(allylamine) hydrochloride as a model system, we demonstrate the use of NMR to distinguish between free and bound polymer and to characterize the degree to which the segments of the nanoparticle-wrapping polymer are mobile (loops and tails) versus immobile (trains). Our results show that the polymer-wrapped nanoparticle contains a large fraction of highly mobile polymer segments, implying that the polymer extends well into solution away from the nanoparticle surface. Flexible, distal polymer segments are likely to be more accessible to extended objects such as cell membranes, compared with polymer segments that are in close proximity to the nanoparticle surface. Thus, these flexible segments may be particularly important in controlling subsequent interactions of the nanoparticles. While reported here for a model system, the methodology used demonstrates how NMR methods can provide important insights into the structure and dynamics at nanoparticle-polymer interfaces, leading to new perspectives on the behavior and interactions of polymer-functionalized nanoparticles in aqueous systems.

Polymer donors of nitric oxide for enhanced accumulation of anticancer agents in solid tumors

This work reported the design, preparation and characterization of functional hollow polymer nanoparticles with S-nitrosothiol (SNO) as scaffolds for nitric oxide (NO) release in PBS buffer and bovine serum. The thiolated hollow polymer nanoparticles were prepared by distillation precipitation polymerization of ethyleneglycol dimethacrylate (EGDMA) and 2-hydroxyethyl methacrylate (HEMA) in presence of 3-(methacryloxy)propyltrimethoxysilane (MPS)-modified silica as seeds and the selective removal of silica core in hydrofluoric acid (HF) aqueous solution together with the subsequent surface esterification of hydroxyl groups with acryloyl chloride to introduce high density of vinyl groups and further Michael addition of carbon–carbon double bonds with hydrosulfide (HS−) anions. S-Nitrosothiol (SNO) functionalized hollow polymer nanoparticles were prepared via nitrosation of the surface thiol groups with acidified nitrite. The releasing characters of SNO-functionalized hollow polymer nanoparticles as NO scaffolds with capacity of 1.55 μmol/mg were investigated in different media, including PBS buffer exposure to trace copper cations and in real bovine serum.

Functionalized PLA-PEG nanoparticles targeting intestinal transporter PepT1 for oral delivery of acyclovir

Targeting intestinal di- and tri-peptide transporter PepT1 with prodrugs is a successful strategy to improve oral drug bioavailability, as demonstrated with valacyclovir, a prodrug of acyclovir. The aim of this new drug delivery strategy is to over-concentrate a poorly absorbed drug on the intestinal membrane surface by targeting PepT1 with functionalized polymer nanoparticles. In the present study, poly(lactic acid)-poly(ethylene glycol)-ligand (PLA-PEG-ligand) nanoparticles were obtained by nanoprecipitation. A factorial experimental design allowed us to identify size-influent parameters and to obtain optimized ≈30nm nanoparticles. Valine, Glycylsarcosine, Valine-Glycine, and Tyrosine-Valine were chemically linked to PLA-PEG. In Caco-2 cell monolayer model, competition between functionalized nanoparticles and [3H]Glycylsarcosine, a strong substrate of PepT1, reduced [3H]Glycylsarcosine transport from 22 to 46%. Acyclovir was encapsulated with a drug load of ≈10% in valine-functionalized nanoparticles, resulting in a 2.7-fold increase in permeability as compared to the free drug. An in vivo pharmacokinetic study in mice compared oral absorption of acyclovir after administration of 25mg/kg of valacyclovir, free or encapsulated acyclovir in functionalized nanoparticles. Acyclovir encapsulation did not statistically modify AUC or Cmax, but increased t1/2 and MRT 1.3-fold as compared to free acyclovir. This new strategy is promising for poorly absorbed drugs by oral administration.

Well-defined single-chain polymer nanoparticles via thiol-Michael addition

A synthetic strategy has been developed giving facile access to well-defined single-chain polymer nanoparticles (SCNPs) from styrene-, acrylate- and methacrylate-based polymers. Random copolymers (polydispersity indices 1.10–1.15) of methyl (meth)acrylate, benzyl methacrylate or styrene containing protected thiol monomers (xanthate and thioacetate vinyl monomers) were obtained via reversible addition–fragmentation chain transfer (RAFT) polymerization. Through aminolysis of the xanthate and thioacetate moieties, copolymers with free thiol moieties were obtained. The thiol bearing polymers were cross-linked with bifunctional acrylates under mild conditions. Precursor polymer dependent size-reductions between 30 and 90% were verified by gel permeation chromatography (GPC) measurements. Furthermore, the SCNPs were characterized by 1H NMR, atomic force microscopy (AFM) and dynamic light scattering (DLS). Characteristic patterns for SCNPs were observed in the AFM phase mode. Thiol-Michael addition is demonstrated to be a versatile tool, which can easily be employed in the preparation of versatile well-defined functional polymer nanoparticles in the 3–10 nm size range.