Ethyl Phosphorylcholine Research Articles

A Visual Distance-Based Capillary Immunoassay Using Biomimetic Polymer Nanoparticles for Highly Sensitive and Specific C-Reactive Protein Quantification.

The low-cost daily monitoring of C-reactive protein (CRP) levels is crucial for screening acute inflammation or infections as well as managing chronic inflammatory diseases. In this study, we synthesized novel 2-Methacryloyloxy ethyl phosphorylcholine (MPC)-based biomimetic nanoparticles with a large surface area to develop a visual CRP-quantification assay using affordable glass capillaries. The PMPC nanoparticles, synthesized via reflux precipitation polymerization, demonstrated multivalent binding capabilities, enabling rapid and specific CRP capture. In the presence of CRP, PMPC nanoparticles formed sandwich structures with magnetic nanoparticles functionalized with CRP antibodies, thereby enhancing detection sensitivity and specificity. These sandwich complexes were magnetically accumulated into visible and quantifiable stacks within the glass capillaries, allowing for the rapid, sensitive, and specific quantification of CRP concentrations with a detection limit of 57.5 pg/mL and a range spanning from 0 to 5000 ng/mL. The proposed visual distance-based capillary biosensor shows great potential in routine clinical diagnosis as well as point-of-care testing (POCT) in resource-limited settings.

Preparation of Water-Soluble Polyion Complex (PIC) Micelles with pH-Responsive Carboxybetaine Block.

A dual zwitterionic diblock copolymer (M100C100) consisting of poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC, M) and poly(3-((2-(methacryloyloxy)ethyl) dimethylammonio) propionate) (PCBMA, C) is synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. A double hydrophilic diblock copolymer (M100S100) consist of PMPC and anionic poly(3-sulfopropyl methacrylate potassium salt) (PMPS, S) is synthesized via RAFT. The degrees of polymerization of each block are 100. The charges of PMPC are neutralized intramolecularly. At neutral pH, the charges in PCBMA are also neutralized intramolecularly due to its carboxybetaine structure. Under acidic conditions, PCBMA exhibits polycation behavior as the pendant carboxy groups become protonated, forming cationic tertiary amine groups. PMPS shows permanent anionic nature independent of pH. Charge neutralized mixture of cationic M100C100 and anionic M100S100 in acidic aqueous solution forms water-soluble polyion complex (PIC) micelle owing to electrostatic attractive interactions. The core is composed of the cationic PCBMA and anionic PMPS blocks, with the PMPC blocks serving as shells that covered the core surface, forming spherical core-shell PIC micelles. Above pH 4 the pendant carboxy groups in PCBMA undergo deprotonation, transitioning to a zwitterionic state, thereby eliminating the cationic charge in PCBMA. Therefore, above pH 4 the PIC micelles are dissociated due to the disappearance of the charge interactions.

Electrochemical Investigation of the Stability of Poly-Phosphocholinated Liposomes.

Poly[2-(methacryloyloxy)ethyl phosphorylcholine] liposomes (pMPC liposomes) gained attention during the last few years because of their potential use in treating osteoarthritis. pMPC liposomes that serve as boundary lubricants are intended to restore the natural lubrication properties of articular cartilage. For this purpose, it is important that the liposomes remain intact and do not fuse and spread as a lipid film on the cartilage surface. Here, we investigate the stability of the liposomes and their interaction with two types of solid surfaces, gold and carbon, by using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). With the aid of a hydrophilic species used as an electroactive probe in the solution, the charge transfer characteristics of the electrode surfaces are obtained. Additionally, from EIS, the capacitance characteristics of the surfaces are derived. No decrease of the peak currents and no displacement of the peak potentials to greater overpotentials are observed in the CV experiments. No decrease in the apparent capacitance and increase in the charge transfer resistance is observed in the EIS experiments. On the contrary, all parameters in both CV and EIS do change in the opposite direction. The obtained results confirm that there is only physical adsorption without fusion and spreading of the pMPC liposomes and without the formation of lipid films on the surfaces of both gold and carbon electrodes.

In‐situ Construction of Self‐Healing Polyelectrolyte/Polyzwitterion Coacervate Framework for High‐Performance Silicon Anodes

AbstractSilicon is considered as a promising candidate for anode materials due to its ultrahigh theoretical capacity and natural abundance. However, the commercialization is severely hampered by the large strain and short cycle life. Herein, we have synthesized a reversible polyelectrolyte/polyzwitterion coacervate framework to achieve high‐performance silicon anodes with high initial Coulombic efficiency (ICE) and stable cyclability. Such coacervate framework is formed via in‐situ free radical polymerization of zwitterionic 2‐methacryloyloxy ethyl phosphorylcholine (MPC) with polyacrylic acid (pAA) during heating the slurry. The resulting pAA/pMPC coacervate framework presents excellent adhesion, thermal stability, and negligible swelling in the electrolyte. Comparing with pAA, pAA/pMPC0.1 coacervate framework binder exhibits superior performance during charge/discharge. The ICE is improved from 84.41 %, to 87.61 %. After 250 cycles, the specific capacity of pAA/pMPC0.1 silicon anode is 1678 mAh g−1 with a retention of 78 % while the pAA silicon anode completely failed after less than 200 cycles. Such improvement is ascribed to the structural integrity of the electrode endowed by the self‐healing ability of pAA/pMPC coacervate framework. This work not only offers a feasible method to in‐situ construct coacervate framework with self‐healing capability to achieve high‐performance silicon anodes but also a compatible electrode preparation process for other high‐capacity materials.

Effect of Added Salt on the RAFT Polymerization of 2-Hydroxyethyl Methacrylate in Aqueous Media.

We report the effect of added salt on the reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-hydroxyethyl methacrylate (HEMA) in aqueous media. More specifically, poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC26) was employed as a salt-tolerant water-soluble block for chain extension with HEMA targeting PHEMA DPs from 100 to 800 in the presence of NaCl. Increasing the salt concentration significantly reduces the aqueous solubility of both the HEMA monomer and the growing PHEMA chains. HEMA conversions of more than 99% could be achieved within 6 h at 70 °C regardless of the NaCl concentration when targeting PMPC26-PHEMA800 vesicles at 20% w/w solids. Significantly faster rates of polymerization were observed at higher salt concentration owing to the earlier onset of micellar nucleation. Transmission electron microscopy (TEM) was used to construct a pseudo-phase diagram for this polymerization-induced self-assembly (PISA) formulation. High-quality images required cross-linking of the PHEMA chains with glutaraldehyde prior to salt removal via dialysis. Block copolymer spheres, worms, or vesicles can be accessed at any salt concentration up to 2.5 M NaCl. However, only kinetically trapped spheres could be obtained in the presence of 3 M NaCl because the relatively low HEMA monomer solubility under such conditions leads to an aqueous emulsion polymerization rather than an aqueous dispersion polymerization. In this case, dynamic light scattering studies indicated a gradual increase in z-average diameter from 26 to 86 nm when adjusting the target PHEMA degree of polymerization from 200 to 800. When targeting PMPC26-PHEMA800 vesicles, increasing the salt content up to 2.5 M NaCl leads to a systematic reduction in the z-average diameter from 953 to 92 nm. Similarly, TEM analysis and dispersion viscosity measurements indicated a gradual reduction in worm contour length with increasing salt concentration for PMPC26-PHEMA600 worms. This new PISA formulation clearly illustrates the importance of added salt on aqueous monomer solubility and how this affects (i) the kinetics of polymerization, (ii) the morphology of the corresponding diblock copolymer nano-objects, and (iii) the mode of polymerization in aqueous media.

Biocompatible Solutions: Evaluating the Safety of Repeated Intra-Articular Injections of pMPCylated Liposomes for Knee Osteoarthritis Therapy in Rat Models.

Knee osteoarthritis (OA) poses a significant health care burden globally, necessitating innovative therapeutic approaches. CCoat, a novel poly(2-[methacryloyloxy]ethyl phosphorylcholine) (pMPC)ylated liposome device, protects the cartilage surface of the joint from mechanical wear through an entropy-favored process. Two preclinical studies were performed to explore the safety of CCoat following repeated intra-articular (IA) injections into the knee joint (i.e., femorotibial joint) in Sprague-Dawley rats. The studies involved 2 or 3 IA injections, at an interval of 2 or 3 weeks, and an observation period of 1 or 13 weeks after the last injection. Assessments included clinical, histopathological, and immunofluorescent evaluations. In study 1, no mortality or abnormal clinical signs occurred. At 1 week post last injection, histopathology revealed minimal vacuolated macrophages beneath the synovial membrane, predominantly M2-like, indicating a nonadverse response. Immunofluorescent staining supported M2-like macrophage predominance. Study 2 confirmed these findings with no systemic effects over 13 weeks. Statistical analyses indicated no significant differences in body weight, clinical pathology, or organ weights compared with controls. Results affirming the safety of pMPCylated liposomes following repeated IA injections in rat. This novel lubricant coating approach shows promise in OA therapy, with this safety assessment supporting its potential clinical application.

Bioinspired zwitterionic triblock copolymers designed for colloidal drug delivery: 2 - Biological evaluation

In this work, poly(lactide) nanoparticles were equipped with a bioinspired coating layer based on poly[2-(methacryloyloxy)ethyl phosphorylcholine] and then evaluated when administered to the lungs and after intravenous injection. Compared to the plain counterparts, the chosen zwitterionic polymer shell prevented the coated colloidal formulation from aggregation and conditioned it for lower cytotoxicity, protein adsorption, complement activation and phagocytic cell uptake. Consequently, no interference with the biophysical function of the lung surfactant system could be detected accompanied by negligible protein and cell influx into the bronchoalveolar space after intratracheal administration. When injected into the central compartment, the coated formulation showed a prolonged circulation half-life and a delayed biodistribution to the liver. Taken together, colloidal drug delivery vehicles would clearly benefit from the investigated poly[2-(methacryloyloxy)ethyl phosphorylcholine]-based polymer coatings.

Bioinspired zwitterionic triblock copolymers designed for colloidal drug delivery: 1 — Synthesis and characterization

This study describes the synthesis and characterization of triblock copolymers composed of poly[2-(methacryloyloxy)ethyl phosphorylcholine]-block-poly(propylene glycol)-block-poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC-b-PPG-b-PMPC) intended for, but not limited to, applications in colloidal drug delivery. Atom transfer radical polymerization led to a library of well-defined PMPC-b-PPG-b-PMPC triblock copolymers with varying overall molecular weight (ranging from ∼5 to ∼25 kDa) and composition (weight fraction of the hydrophobic PPG block ranged from ∼10 to ∼50 wt%). The properties of the synthesized triblock copolymers were linked to the PPG to bioinspired PMPC block(s) ratio, where the more hydrophilic species showed adequate aqueous solubility, surface activity and biocompatibility (non-toxicity) in in vitro cell culture. Their amphiphilic nature makes them adsorb efficiently onto polymer nanoparticles, what improves colloidal stability under stress conditions and, furthermore, depletes proteins from unwanted adsorption to the underlying surface. The current findings strengthen our insights into structure-function relationships of PMPC-based coatings leading to protecting shells on relevant polymer nanoparticle formulations. PMPC-b-PPG-b-PMPC triblock copolymers composed of a hydrophobic PPG block of 2–4 kDa flanked by two hydrophilic PMPC blocks each of 5–10 kDa seem to be most promising to enhance colloidal drug delivery vehicles.

Comparison study of surface-initiated hydrogel coatings with distinct side-chains for improving biocompatibility of polymeric heart valves.

Polymeric heart valves (PHVs) present a promising alternative for treating valvular heart diseases with satisfactory hydrodynamics and durability against structural degeneration. However, the cascaded coagulation, inflammatory responses, and calcification in the dynamic blood environment pose significant challenges to the surface design of current PHVs. In this study, we employed a surface-initiated polymerization method to modify polystyrene-block-isobutylene-block-styrene (SIBS) by creating three hydrogel coatings: poly(2-methacryloyloxy ethyl phosphorylcholine) (pMPC), poly(2-acrylamido-2-methylpropanesulfonic acid) (pAMPS), and poly(2-hydroxyethyl methacrylate) (pHEMA). These hydrogel coatings dramatically promoted SIBS's hydrophilicity and blood compatibility at the initial state. Notably, the pMPC and pAMPS coatings maintained a considerable platelet resistance performance after 12 h of sonication and 10 000 cycles of stretching and bending. However, the sonication process induced visible damage to the pHEMA coating and attenuated the anti-coagulation property. Furthermore, the in vivo subcutaneous implantation studies demonstrated that the amphiphilic pMPC coating showed superior anti-inflammatory and anti-calcification properties. Considering the remarkable stability and optimal biocompatibility, the amphiphilic pMPC coating constructed by surface-initiated polymerization holds promising potential for modifying PHVs.

Lipidure-based micropattern fabrication for stereotyping cell geometry

Cell autonomous behaviors such as migration and orchestration of cell polarity programs are required for physiological tissue formation. Micropatterns are cell-adhesive shapes that confine cell(s) to a user defined geometry. This biophysical confinement allows researchers to standardize the cell shape, and in doing so, stereotype organelle and cytoskeletal systems that can have an arbitrary organization. Thus, micropatterning can be a powerful tool in interrogation of polarity programs by enforcing a homogenous cell shape and cytoskeletal organization. A major drawback of this approach is the equipment and reagent costs associated with fabrication. Here, we provide a characterization of a compound called Lipidure (2-Methacryloyloxy ethyl phosphorylcholine) that is up to 40X less expensive than other cell repulsive coating agents. We found that Lipidure is an effective cell-repulsive agent for photolithography-based micropattern fabrication. Our results demonstrate that Lipidure is sensitive to deep UV irradiation for photolithography masking, stable in both benchtop and aqueous environments, non-toxic in prolonged culture, and effective at constraining cell geometry for quantification of cytoskeletal systems.

The Sequential and Systemic Administration of BMP-2 and SDF-1α Nanocapsules for Promoting Osteoporotic Fracture Healing.

The objective of this study was to investigate the use of the nanocapsule sequential delivery of BMP-2 and SDF-1α through the peripheral circulatory system to promote the healing of osteoporotic fractures. Based on increased vascular permeability in the early hematoma environment around the fracture and the presence of a large number of matrix metalloproteinase MMPs in the inflammatory environment, we designed MMP-sensitive nanocapsules which were formed viain situ free-radical polymerization on the surface of grow factors with 2-(methacryloyloxy) ethyl phosphorylcholine (MPC) and the bisacryloylated VPLGVRTK peptide. The antiphagic effect and biological activity of the growth factors for the nanomicrocapsule delivery system were tested by cell experiments. The 36 SD rats with an osteoporotic fracture model were randomly divided into six groups (A, B, C, D, E, and F). In this paper, the nanocapsules loaded with BMP-2 and SDF-1 are represented as n (BMP-2) and n (SDF-1α). In the six groups, the following different combinations of growth factors were injected into the bone defect site on days 1 and 3 after bone defect surgery: in group A, n (SDF-1α) combined with n (SDF-1α); in group B, n (BMP-2) combined with n (BMP-2); in group C, n (SDF-1α) + n (BMP-2) combined with n (SDF-1α) + n (BMP-2); in group D, n (SDF-1α) combined with n (BMP-2); in group E, n (BMP-2) combined with n (SDF-1α); in group F, nanocapsules without growth factor were used as the control group. Micro-CT was used to observe the effect of n(BMP-2) and n(SDF-1α) sequential delivery inearly healing in osteoporotic fractures. Finally, in this study, we evaluated the safety of the nanocapsules delivery system by detecting ectopic osteogenesis and inflammatory responses in animals. Nanocapsules have low toxicity and protect the integrity and biological activity of growth factors. The results confirmed that nanocapsules could still be effectively targeted to the fracture site on days 1, 3, and 7 after intravenous administration. Growth factors encapsulated in nanocapsules have better bone repair results than natural growth factors. In particular, groups C and D had the best bone repair results than other groups.In vivo experiments confirmed that nanocapsules did not cause significant ectopic osteogenesis and inflammation. The results confirmed that the special vascular permeability and inflammatory factor microenvironment of the fracture site could be used to deliver two growth factors with a synergistic effect through venous circulation, which could better promote the healing process of osteoporotic fracture.

Hemocompatibility of β-Cyclodextrin-Modified (Methacryloyloxy)ethyl Phosphorylcholine Coated Magnetic Nanoparticles.

Adsorbing toxins from the blood to augment membrane-based hemodialysis is an active area of research. Films composed of β-cyclodextrin-co-(methacryloyloxy)ethyl phosphorylcholine (p(PMβCD-co-MPC)) with various monomer ratios were formed on magnetic nanoparticles and characterized. Surface chemistry effects on protein denaturation were evaluated and indicated that unmodified magnetic nanoparticles greatly perturbed the structure of proteins compared to coated particles. Plasma clotting assays were conducted to investigate the stability of plasma in the presence of particles, where a 2:2 monomer ratio yielded the best results for a given total surface area of particles. Total protein adsorption results revealed that modified surfaces exhibited reduced protein adsorption compared to bare particles, and pure MPC showed the lowest adsorption. Immunoblot results showed that fibrinogen, α1-antitrypsin, vitronectin, prekallikrein, antithrombin, albumin, and C3 correlated with film composition. Hemocompatibility testing with whole blood illustrated that the 1:3 ratio of CD to MPC had a negative impact on platelets, as evidenced by the increased activation, reduced response to an agonist, and reduced platelet count. Other formulations had statistically significant effects on platelet activation, but no formulation yielded apparent adverse effects on hemostasis. For the first time, p(PMβCD-co-MPC)-coated MNP were synthesized and their general hemocompatibility assessed.

A resin adhesive with balanced antibacterial and mineralization properties for improved dental restoration

ObjectiveAiming to develop an adhesive formulation that achieves a harmonious equilibrium between antibacterial efficacy and mineralization potential, 2-methacryloyloxy ethyl phosphorylcholine (MPC), N,N-dodecylvinylimidazole (DCV), and Sr-doped hydroxyapatite (Sr/HAp) nanorods were incorporated as functional constituents into the adhesive matrix, employing carefully optimized proportions. MethodsThe adhesive formulation comprised a blend of bisphenol A glycerolate dimethacrylate (Bis-GMA), 2-hydroxyethyl methacrylate (HEMA), and 1,6-hexanediol dimethacrylate (HDDMA) monomers. The effects of MPC and DCV additions, ranging from 1% to 4% (wt%), on various aspects such as adhesive curing kinetics, bonding strength, water contact angle, mechanical properties, and antibacterial activities against Streptococcus mutans (S. mutans) and Human Saliva Bacterial Flora (HSBF), was investigated both individually and in combination. Following the determination of the optimized MPC/DCV ratio, the effect of Sr/HAp on the mineralization potential of the adhesives was evaluated by soaking the samples in 1.5 times simulated body fluid (SBF) at 37 °C for 3 days followed by examination using scanning electron microscopy (SEM). Additionally, biocompatibility assay was conducted using L929 fibroblasts. ResultsThe introduction of MPC and DCV did not interfere the CC conversion degree of the resin blends in all the preparations. Notably, the incorporation of 3 wt% MPC demonstrated a significantly enhancement in the hydrophilicity of the adhesive, resulting in reduced bacterial adsorption. The addition of 3 wt% DCV exhibited potent antibacterial properties against attached bacteria. Furthermore, the introduction of 8 wt% Sr/HAp displayed a positive effect on mineral deposition on the adhesive surface. Importantly, all adhesive formulations demonstrated negligible cytotoxicity. Although a decrease in bonding strength was observed upon the introduction of MPC/DCV, the supplementation of Sr/HAp exhibited a reinforcing effect, effectively compensating for the decline. This beneficial outcome can be attributed to a substantial improvement in the flexural strength/modulus of the composite adhesive. SignificanceThe adhesive, simultaneously having ability in inhibiting bacteria adsorption, killing bacteria and promoted mineralization, holds great potential in achieving strong bonding strength for dental restoration applications to minimize repair failure.

Preparation of Water-Soluble Polyion Complex (PIC) Micelles with Random Copolymers Containing Pendant Quaternary Ammonium and Sulfonate Groups.

Cationic random copolymers (PCm) consisting of 2-(methacryloyloxy)ethyl phosphorylcholine (MPC; P) with methacroylcholine chloride (MCC; C) and anionic random copolymers (PSn) consisting of MPC and potassium 3-(methacryloyloxy)propanesulfonate (MPS; S) were prepared via a reversible addition-fragmentation chain transfer method. "m" and "n" represent the compositions (mol %) of the MCC and MPS units in the copolymers, respectively. The degrees of polymerization for the copolymers were 93-99. Water-soluble MPC unit contains a pendant zwitterionic phosphorylcholine group whose charges are neutralized in pendant groups. MCC and MPS units contain the cationic quaternary ammonium and anionic sulfonate groups, respectively. The stoichiometrically charge-neutralized mixture of a matched pair of PCm and PSn aqueous solutions resulted in the spontaneous formation of water-soluble PCm/PSn polyion complex (PIC) micelles. These PIC micelles have the MPC-rich surface and MCC/MPS core. These PIC micelles were characterized using 1H NMR, dynamic and static light scattering, and transmission electron microscopic measurements. The hydrodynamic radius of these PIC micelles depends on the mixing ratio of the oppositely charged random copolymers. The charge-neutralized mixture formed maximum-size PIC micelles.

Zwitterion Functionalized Graphene Oxide/Polyacrylamide/Polyacrylic Acid Hydrogels with Photothermal Conversion and Antibacterial Properties for Highly Efficient Uranium Extraction from Seawater

AbstractIn this study, graphene oxide (GO) and polyacrylamide/polyacrylic acid (PAM/PAA) are used to prepare hydrogels with photothermal conversion properties for highly efficient uranium extraction from seawater. Zwitterionic 2‐methacryloyloxy ethyl phosphorylcholine (MPC) is introduced in the PAM/PAA/GO hydrogel to obtain PAM/PAA/GO/MPC (PAGM), exhibiting good antibacterial properties. PAGM demonstrates efficient and specific adsorption of uranium (VI) (U(VI)). Under light conditions, the adsorption capacity of PAGM reaches 196.12 mg g−1 (pH = 8, t = 600 min, C0 = 99.8 mg L−1, m/v = 0.5 g L−1). The adsorption capacity is only 160.29 mg g−1 under dark conditions (pH = 8, t = 600 min, C0 = 99.8 mg L−1, m/v = 0.5 g L−1). The adsorption capacity of light is 22.5% higher than that of dark. The adsorption process is fitted using the Langmuir and pseudo‐second‐order models. Furthermore, PAGM exhibits good repeatability and stability after five adsorption–desorption cycles. PAGM exhibits a U(VI) adsorption capacity of 6.1 mg g−1 after storage for one month in natural seawater. The X‐ray photoelectron spectroscopy (XPS) results demonstrate that the coordination of the amino, carboxyl, and hydroxyl groups with U(VI) is the primary mechanism of U(VI) adsorption. The mechanism is confirmed through detailed density functional theory calculations. PAGM demonstrates durability, high efficiency, photothermal conversion properties, and antibacterial properties. Thus, it is a promising candidate for uranium extraction from seawater.

Water Soluble PMPC-Derived Bright Fluorescent Nitrogen/Phosphorous-Doped Carbon Dots for Fluorescent Ink (Anti-Counterfeiting) and Cellular Multicolor Imaging.

Here, a simple one-step hydrothermal-assisted carbonization process was adopted for the preparation of nitrogen/phosphorous-doped carbon dots from a water-soluble polymer, poly 2-(methacryloyloxy)ethyl phosphorylcholine (PMPC). By the free-radical polymerization method, PMPC was synthesized using 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) and 4,4'-azobis (4-cyanovaleric acid). The water-soluble polymers, PMPC, that have nitrogen/phosphorus moieties are used to prepare carbon dots (P-CDs). The resulting P-CDs were thoroughly characterized by various analytical techniques such as field emission-scanning electron microscopy (FESEM) with energy-dispersive X-ray spectroscopy (EDS), high-resolution transmittance electron microscopy (HRTEM), X-ray diffraction (XRD), Raman spectroscopy, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), Ultraviolet-visible (UV-vis) spectroscopy and fluorescence spectroscopy to determine their structural and optical properties. The synthesized P-CDs displayed bright/durable fluorescence, were stable for long periods, and confirmed the enrichment of functionalities including oxygen, phosphorus, and nitrogen heteroatoms in the carbon matrix. Since the synthesized P-CDs showed bright fluorescence with excellent photostability, excitation-dependent fluorescence emission, and excellent quantum yield (23%), it has been explored as a fluorescent (security) ink for drawing and writing (anti-counterfeiting). Further, cytotoxicity study results advised for biocompatibility and thus were used for cellular multicolor imaging in nematodes. This work not only demonstrated the preparation of CDs from polymers that can be used as advanced fluorescence ink, a bioimaging agent for anti-counterfeiting, and cellular multicolor imaging candidate, but additionally prominently opened a new perspective on the bulk preparation of CDs simply and efficiently for various applications.

Decorated small intestinal submucosa (SIS) based bio-patch with anti-fouling and vascularized capacity to accelerate chronic wound regeneration via TGF-β and MAPK pathway

Chronic wounds in diabetes take a lifetime risk of developing into diabetic foot ulcers (DFUs). Conventional wound dressings and commercial products fail for ideal tissue regeneration in DFUs due to the incapacity to promote vascularization and prevent bacterial infections during wound repair. In this study, the small intestinal submucosa (SIS) with enriched vascularized bioactive factors, was chemically decorated by 2-methacryloyloxy ethyl phosphorylcholine (MPC) through Michael-type addition to be endowed anti-fouling ability, in order to treat chronic wound regeneration in diabetes. In the diabetic skin injury experiment, we established the animal model by 5-mm diameter defects in the SD rats and implanted the bio-patches to the located sites. The SIS-MPC bio-patch showed superior advantages in bacterial anti-adhesion (100-fold foul resistance than commercial patches), while maintained affinity for fibroblast growth and collagen formation, as demonstrated by immunohistochemical staining from the local tissues, outperforming commercial wound dressings in tissue regeneration, which was attributed to acceleration in neovascularization and inflammation modulation through TGF-β and MAPK pathway. This novel SIS-MPC bio-patch would be a promising candidate for medical translations into diabetes and chronic wound treatments.

Synthesis of High Molecular Weight Water-Soluble Polymers as Low-Viscosity Latex Particles by RAFT Aqueous Dispersion Polymerization in Highly Salty Media.

We report the synthesis of sterically-stabilized diblock copolymer particles at 20% w/w solids via reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of N,N′-dimethylacrylamide (DMAC) in highly salty media (2.0 M (NH4)2SO4). This is achieved by selecting a well-known zwitterionic water-soluble polymer, poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC), to act as the salt-tolerant soluble precursor block. A relatively high degree of polymerization (DP) can be targeted for the salt-insoluble PDMAC block, which leads to the formation of a turbid free-flowing dispersion of PDMAC-core particles by a steric stabilization mechanism. 1H NMR spectroscopy studies indicate that relatively high DMAC conversions (>99%) can be achieved within a few hours at 30 °C. Aqueous GPC analysis indicates high blocking efficiencies and unimodal molecular weight distributions, although dispersities increase monotonically as higher degrees of polymerization (DPs) are targeted for the PDMAC block. Particle characterization techniques include dynamic light scattering (DLS) and electrophoretic light scattering (ELS) using a state-of-the-art instrument that enables accurate ζ potential measurements in a concentrated salt solution. 1H NMR spectroscopy studies confirm that dilution of the as-synthesized dispersions using deionized water lowers the background salt concentration and hence causes in situ molecular dissolution of the salt-intolerant PDMAC chains, which leads to a substantial thickening effect and the formation of transparent gels. Thus, this new polymerization-induced self-assembly (PISA) formulation enables high molecular weight water-soluble polymers to be prepared in a highly convenient, low-viscosity form. In principle, such aqueous PISA formulations are highly attractive: there are various commercial applications for high molecular weight water-soluble polymers, while the well-known negative aspects of using a RAFT agent (i.e., its cost, color, and malodor) are minimized when targeting such high DPs.

Designer Liposomic Nanocarriers Are Effective Biofilm Eradicators.

Drug delivery via nanovehicles is successfully employed in several clinical settings, yet bacterial infections, forming microbial communities in the form of biofilms, present a strong challenge to therapeutic treatment due to resistance to conventional antimicrobial therapies. Liposomes can provide a versatile drug-vector strategy for biofilm treatment, but are limited by the need to balance colloidal stability with biofilm penetration. We have discovered a liposomic functionalization strategy, using membrane-embedded moieties of poly[2-(methacryloyloxy)ethyl phosphorylcholine], pMPC, that overcomes this limitation. Such pMPCylation results in liposomic stability equivalent to current functionalization strategies (mostly PEGylation, the present gold-standard), but with strikingly improved cellular uptake and cargo conveyance. Fluorimetry, cryo-electron, and fluorescence microscopies reveal a far-enhanced antibiotic delivery to model Pseudomonas aeruginosa biofilms by pMPC-liposomes, followed by faster cytosolic cargo release, resulting in significantly greater biofilm eradication than either PEGylation or free drug. Moreover, this combination of techniques uncovers the molecular mechanism underlying the enhanced interaction with bacteria, indicating it arises from bridging by divalent ions of the zwitterionic groups on the pMPC moieties to the negatively charged lipopolysaccharide chains emanating from the bacterial membranes. Our results point to pMPCylation as a transformative strategy for liposomal functionalization, leading to next-generation delivery systems for biofilm treatment.

Preclinical In Vivo Safety of Poly-Phosphorylated Superlubrication Vectors for the Treatment of Osteoarthritis.

Osteoarthritis (OA) can lead to a significant functional disability. Poly[2-(methacryloyloxy)ethyl phosphorylcholine] (pMPC) liposomes are a novel treatment modality for OA, intended to restore the natural lubrication properties of articular cartilage. Here, we report on two studies aimed to assess the local and systemic safety and toxicity of pMPCylated liposomes in comparison with physiological saline, in Sprague-Dawley (SD) rats and in sheep after a single intra-articular (IA) injection. The animals were sacrificed after 1 and 6 weeks (rats) and 3 and 6 weeks (sheep). No signs of toxicity or abnormal clinical findings were observed. Histopathological evaluation revealed no signs of reactivity or abnormal findings in the injected joints or in any other organs. In conclusion, a single IA injection of the pMPCylated liposomes demonstrated an excellent safety profile and did not result in local reactivity or systemic toxicity, thus supporting its further development for use in humans.