Monodisperse Poly Ethylene Research Articles

Preparation of chiral polyether dendrimer and its non-bonding immobilized CALB for high enantioselective synergy resolution of amines

Monodisperse polyethylene glycol monomethyl ether and chiral glycidyl tosylate were utilized as substrates in the synthesis of the chiral monomer unit epoxypropyl polyethylene glycol monomethyl ether (MPEGn-EPO). The initiator propargyl-terminated polyethylene glycol alkyne-PEG3-OH was employed, while the phosphazene base P4-t-Bu facilitated the controlled ROP of MPEGn-EPO, resulting in clickable dendritic P(MPEGn-EPO) with terminal alkyne. The chiral four-arm dendritic polymer 4-Arm-PEG3-Mn was synthesized through a click reaction between 4-Arm-PEG3-N3 and P(MPEGn-EPO) using Cu(PPh3)3Br/CuBr as a catalyst. Candida antarctica lipase B (CALB) was chosen as a model enzyme for the preparation of a non-covalently immobilized biocatalyst (CALB-M) via a simple adsorption process with magnesium silicate and 4-Arm-PEG3-M4-20. The immobilized lipase CALB-M16 demonstrated high enzyme activity in the resolution of racemic amines, yielding chiral amines with enantioselectivity up to 99 % ee. Circular dichroism (CD) analysis indicated the formation of helical conformation in the dendritic polyethers 4-Arm-PEG3-M16-20 in the presence of magnesium silicate at 5 °C. The polyethylene glycol side groups of 4-Arm-PEG3-M16-20 are suggested to potentially form a crown ether-like structure with magnesium ions, which could enhance steric hindrance and induce a right-handed helix. Furthermore, the helical structure of this dendritic polyether is thought to work in synergy with CALB, improving the enantioselective resolution of amines.

Impact of N-Terminal PEGylation on Synthesis and Purification of Peptide-Based Cancer Epitopes for Pancreatic Ductal Adenocarcinoma (PDAC).

Peptide-based cancer vaccines have shown promising results in preclinical trials focusing on tumor immunotherapy. However, the presence of hydrophobic amino acid segments within these peptide sequences poses challenges in their synthesis, purification, and solubility, thereby hindering their potential use as cancer vaccines. In this study, we successfully synthesized peptide sequences derived from mesothelin (MSLN), a tumor-associated antigen overexpressed in pancreatic ductal adenocarcinoma (PDAC) by conjugating them with monodisperse polyethylene glycol (PEG). By PEGylating mesothelin epitopes of varying lengths (ranging from 9 to 38 amino acids) and hydrophobicity (60-90%), we achieved an effective method to improve the peptide yield and facilitate the processes of synthesis and purification. PEGylation significantly enhanced the solubility, facilitating the single-step purification of lengthy hydrophobic peptides. Most importantly, PEGylation did not compromise cell viability and had little to no effect on the immunogenicity of the peptides. In contrast, the addition of a palmitoyl group to increase immunogenicity led to reduced yield and solubility. Overall, PEGylation proves to be an effective technique for enhancing the solubility and broadening the range of utility of diverse long hydrophobic peptides.

Monodispersed biodegradable microparticles with wrinkled surface coated with silver nanoparticles for catalytic degradation of organic toxins

AbstractMicrofluidic fabrication of monodisperse microgels for biomedical, nanotechnological, environmental, and catalytic applications has become the subject of growing interest. In this work, monodisperse polyethylene glycol diacrylate [P(EGDA)] microgel particles were fabricated using a CNC-milled microfluidic device with a Lego-inspired interlocking mechanism. Silver nanoparticles (AgNPs) were synthesised and stabilised in situ on the wrinkled surface of the microgel particles using AgNO3 as a metal precursor and NaBH4 as a reductant. The loading of AgNPs (7.5 wt%) on microgel beads was confirmed by energy-dispersive X-ray spectroscopy, X-ray diffraction, and thermogravimetric analysis. Surface wrinkles were found to be a useful morphological feature acting as reservoirs for the accumulation of AgNPs. Ag–P(EGDA) hybrid polymer particles were shown to be an efficient catalyst for the reduction of 4-nitrophenol (4NP) into 4-aminophenol (4AP) by sodium borohydride at room temperature. After 40 min, 0.08 M 4NP was completely converted into 4AP using 2.1 mg/mL of Ag–P(EGDA) catalytic particles, and the reaction followed a pseudo-first-order kinetics. The apparent rate constant increased from 0.0142 to 0.117 min−1 when the loading of catalytic particles increased from 1.7 to 2.50 mg/mL indicating that the reduction is occurring on the catalyst surface according to the Langmuir–Hinshelwood model. Ag–P(EGDA) hybrid microgel was a potent and recyclable catalyst for room-temperature degradation of methylene blue (MeB) by NaBH4. At the Ag–P(EGDA) loading of 2.0 mg/mL, 25 µM of MeB was completely degraded in 6 min. Composite Ag–P(EGDA) microgel beads can be used as an eco-friendly and easily recoverable catalyst for the transformation of other organic pollutants into useful chemicals. Graphical abstract

Molecular Processes Leading to Shear Banding in Entangled Polymeric Solutions.

The temporal and spatial evolution of shear banding during startup and steady-state shear flow was studied for solutions of entangled, linear, monodisperse polyethylene C3000H6002 dissolved in hexadecane and benzene solvents. A high-fidelity coarse-grained dissipative particle dynamics method was developed and evaluated based on previous NEMD simulations of similar solutions. The polymeric contribution to shear stress exhibited a monotonically increasing flow curve with a broad stress plateau at intermediate shear rates. For startup shear flow, transient shear banding was observed at applied shear rates within the steady-state shear stress plateau. Shear bands were generated at strain values where the first normal stress difference exhibited a maximum, with lifetimes persisting for up to several hundred strain units. During the lifetime of the shear bands, an inhomogeneous concentration distribution was evident within the system, with higher polymer concentration in the slow bands at low effective shear rate; i.e., γ˙<τR-1, and vice versa at high shear rate. At low values of applied shear rate, a reverse flow phenomenon was observed in the hexadecane solution, which resulted from elastic recoil of the molecules within the slow band. In all cases, the shear bands dissipated at high strains and the system attained steady-state behavior, with a uniform, linear velocity profile across the simulation cell and a homogeneous concentration.

The effects of gold nanoparticles with different surface coatings and sizes on biochemical parameters in mice

Objectives: Gold nanoparticles are very popular metallic nanomaterials and they have a wide spectrum of biomedical applications. This study was aimed to the production of stable and monodisperse polyethyleneimine (PEI) and polyethylene glycol (PEG) coated gold nanoparticles (AuNP20 and AuNP50), investigation of their in vivo biochemical effects in the BALB/c mice. Methods: Gold nanoparticles were synthesized and their surfaces were modified by PEI and PEG. All the necessary physicochemical characterizations were performed. After the single high dose i.v. injection (5 mg Au/kg animal weight) of the AuNP groups, their in vivo biochemical effects were evaluated multiparametrically in the mice on day 14. Results: Highly monodisperse and stable AuNPs were synthesized successfully. Significant changes in the biochemical hemogram parameters were observed depending on the surface coatings of the AuNPs. PEI and PEG surface coatings increased biocompatibility. No excessive oxidative stress response was observed in all the gold nanoparticle groups. Conclusions: It has been concluded that the surface chemistry of the particles is a more decisive parameter than the size in terms of in vivo biochemical toxicity. The surface functionalization, stability and biocompatibility of the AuNPs are important parameters for the potential biomedical applications of gold nanoparticles in future studies.

Microstructural evolution and reverse flow in shear-banding of entangled polymer melts.

The temporal and spatial evolution of shear banding under startup of shear flow was simulated for highly entangled, linear, monodisperse polyethylene melts of differing molecular weight, C750H1502, C1200H2402, and C3000H6002, using a high-fidelity coarse-grained dissipative particle dynamics method. It was determined that shear stress was dominated by segmental orientation of entangled strands at low shear rates, but at a critical shear rate below the reciprocal of the Rouse time, flow-induced disentanglement resulted in the onset of chain tumbling that reduced the average degree of orientation, leading to a regime of decreasing shear stress, with a commensurate onset of increasing average chain extension imposed by the strong flow kinematics that ultimately drove the steady-state shear stress higher. During startup of shear flow, shear band development began immediately after the maximum in the first normal stress difference, where distinct fast and slow bands formed. The slow bands consisted of relatively entangled and coiled molecules, whereas the fast bands consisted of more disentangled and extended chains that experienced quasiperiodic rotation/retraction cycles. The simulation results often exhibited a generation of temporary reverse flow, in which the local fluid velocity was temporarily opposite to that of the bulk flow direction, at the onset of the shear-banding phenomena; this effect was consistent with earlier experiments and theoretical results. The physical mechanism for the generation of reverse flow during shear-band formation was investigated and found to be related to the recoil of the molecules comprising the slow band. Overall, the phenomenon of shear banding appeared to arise due to flow-induced disentanglement from orientational ordering and segmental stretching that affected individual chains to different degrees, ultimately resulting in regions of relatively coiled and entangled chains that evolved into a slow band, whereas the locally disentangled chains, experiencing quasiperiodic stretch-rotation cycles, formed a fast band. The transitional period resulted in a kinematic instability that generated the temporary reverse-flow phenomenon.

Controllable Fabrication and Oil–Water Separation Properties of Polyethylene Terephthaloyl-Ethylenediamine-IPN-poly(N-Isopropylacrylamide) Microcapsules

In this paper, we report a microcapsule embedded PNIPAN in P (TPC-EDA) shell and it can be regarded as an interpenetrating polymer network (IPN) structure, which can accelerate the penetration of oily substances at a certain temperature, and the microcapsules are highly monodisperse and dimensionally reproducible. The proposed microcapsules were fabricated in a three-step process. The first step was the optimization of the conditions for preparing oil in water emulsions by microfluidic device. In the second step, monodisperse polyethylene terephthaloyl-ethylenediamine (P(TPC-EDA)) microcapsules were prepared by interfacial polymerization. In the third step, the final microcapsules with poly(N-isopropylacrylamide) (PNIPAM)-based interpenetrating polymer network (IPN) structure in P(TPC-EDA) shells were finished by free radical polymerization. We conducted careful data analysis on the size of the emulsion prepared by microfluidic technology and used a very intuitive functional relationship to show the production characteristics of microfluidics, which is rarely seen in other literatures. The results show that when the IPN-structured system swelled for 6 h, the adsorption capacity of kerosene was the largest, which was promising for water-oil separation or extraction and separation of hydrophobic drugs. Because we used microfluidic technology, the products obtained have good monodispersity and are expected to be produced in large quantities in industry.

Pharmacokinetics of fluorobenzyl polyethylene glycol conjugated tetraiodothyroacetic acid (NP751), a novel anticancer thyrointegrin αvβ3 antagonist.

We have recently reported on the development of fb-PMT (NP751), a conjugate of the thyroid hormone metabolite tetraiodothyroacetic acid (tetrac) and monodisperse polyethylene glycol 36. It exhibited high affinity for thyrointegrin αvβ3 receptor and potent anti-angiogenic and anticancer activity in vivo. The objective of the current study is to determine the pharmacokinetics (PK) of fb-PMT in experimental animals, such as mice, rats, and monkeys. NP751 was quantified using a propylene diamine-modified tetraiodothyroacetic acid (DAT) as an internal standard. The limit of quantification (LOQ) for fb-PMT was 1.5ng/μL and the recovery efficiency was 93.9% with the developed method. The peak plasma concentration (Cmax) and the area under the curve (AUC) results at different doses in mice, rats and monkeys suggest that pharmacokinetics of NP751 is dose-dependent within the dose ranges administered. Results indicate that NP751 has comparable PK parameters that provides enough exposure as a molecularly tumor targeted molecule in multiple species and is a promising anticancer therapeutic.

Role of Short Chain Branching in Crystalline Model Polyethylenes

The role of short chain branches (SCBs) (C4H9) on the melt and crystalline properties of monodisperse polyethylene systems (C400H802) is investigated, using molecular dynamics simulations of a coarse-grained united-monomer model that represents a chemical monomer as one particle. A method is introduced, whereby SCBs are grown out of the linear backbone to minimize computational expense. Here, this concept is proven by introducing differing numbers (Nb = 0, 1, 2, 4, 10, and 20) of regularly spaced SCBs along the chain backbones and studying their influence on the melt and crystalline properties. By growing SCBs into the melt phase, it is demonstrated that they marginally perturb the original topology, justifying a relatively short equilibration time after growth. Upon crystallization, however, each system’s behavior differs considerably. Cooling and heating cycles are performed to study crystallization and melting at progressively slower rates. The crystalline morphology is observed to depend strongly on both cooling rate and number of branches along the linear backbone. In particular, the lamella thickness decreases systematically with both faster cooling and increasing SCB content. At the highest branch content, of one per 20 backbone carbons (Nb = 20), crystallization is almost entirely suppressed, whereas a small number of branches allows control over the average lamellar thickness. This observation, combined with a prudent method for equilibrating systems with SCBs, opens up opportunities to study more complex chain architectures and mimic industrial polyethylene morphologies.

Microfluidic Fabrication and Characterization of Radiopaque Barium Sulfate Polyethylene Glycol‐Based Hydrogel Microspheres

The objective of this study was to fabricate and characterize monodisperse polyethylene glycol (PEG)‐based barium sulfate hydrogel microspheres for applications in prostatic hyperplasia and prostate cancer treatments. Currently, catheter embolization procedures used in prostatic hyperplasia treatments employ non‐opaque microspheres with a tracer dye, which can result in off‐target embolization. The goal of this study was to fabricate monodisperse, radiopaque microspheres that can be easily tracked via microcomputed tomography (microCT) during embolization procedures. The hydrogel microspheres were fabricated using 4‐arm PEG‐Acrylate macromer and PEG‐dithiol crosslinker solutions in a custom‐designed microfluidic chip that allowed for on‐chip mixing and gelation of a timed‐gelation system, greatly improving bead fabrication throughput and reproducibility. Microspheres were loaded with 1 μm barium sulfate particles and bovine serum albumin to aid in barium suspension. Microspheres were imaged both before and after washing with buffer using an inverted microscope to measure microsphere diameter and degradation. Settling of barium sulfate solutions was measured qualitatively in microcentrifuge tubes. Monodisperse, barium sulfate loaded‐hydrogel microspheres were produced, the size of which could be controlled by modulating the inlet flow rates of the dispersed and continuous phases. Furthermore, the results show that the opacity of the barium sulfate microspheres increased with increased barium sulfate concentration. In conclusion, the results indicate that this study successfully fabricated monodisperse and opaque barium sulfate PEG‐based hydrogel microspheres. Future experiments will evaluate the radiopacity under microCT, swelling and degradation properties, and injectability of the hydrogel microspheres to help further confirm the application of these microspheres in catheter embolization procedures.

Elucidating the role of network topology dynamics on the coil-stretch transition hysteresis in extensional flow of entangled polymer melts

Dissipative particle dynamics (DPD) simulations are performed on coarse-grained replicas of linear, monodisperse entangled polyethylene melts C1000H2002 and C3000H6002 undergoing both steady-state and transient planar elongational flow (PEF). The fidelity of the DPD simulations is verified by direct comparison of flow topological and rheological properties of a 334-particle chain liquid against the united-atom C1000H2002 liquid, simulated using nonequilibrium molecular dynamics (NEMD). These DPD simulations demonstrate that a flow-induced coil-stretch transition (CST) and its associated hysteresis caused by configurational microphase separation, as observed in previous NEMD simulations of PEF, can be replicated using a more computationally efficient coarse-grained system. Results indicate that the breadth of the CST hysteresis loop is enlarged for the longer molecule liquid relative to the shorter one. Furthermore, relaxation simulations reveal that reducing the applied flow Deborah number (De) from a high value corresponding to a homogeneous phase of highly stretched molecules to a De within the biphasic region results in a two-stage relaxation process. There is a fast initial stratification of the kinetically trapped highly stretched chains into regions of highly extended and less extended chains, which displays similar behavior to a system undergoing a spinodal decomposition caused by spatial configurational free energy fluctuations. After a short induction period of apparently random duration, the less extended chain regions experience a stochastic nucleation event that induces configurational relaxation to domains composed of coiled molecules over a much longer time scale, leaving the more highly extended chains in surrounding sheetlike domains. The time scales of these two relaxation processes are of the same order of magnitude as the Rouse and disengagement times of the equilibrium liquids.

Targeting Thyrointegrin αvβ3 Using Fluorobenzyl Polyethylene Glycol Conjugated Tetraiodothyroacetic Acid (NP751) in Acute Myeloid Leukemia.

BackgroundAcute myeloid leukemia (AML) is associated with poor long-term survival, even with newer therapeutic agents. Here, we show the results of our preclinical study, in which we evaluated the efficacy of a new thyrointegrin αvβ3 antagonist, named fluorobenzyl polyethylene glycol conjugated tetraiodothyroacetic acid (fb-PMT).Methods and Resultsfb-PMT (NP751) is a potent αvβ3 antagonist of molecular weight of 2,478.9 Da. it represents a conjugate of tetraiodothyroacetic acid (tetrac) and monodisperse polyethylene glycol (PEG36), with a 4-fluorobenzyl group capping the other end of the PEG. fb-PMT effectively suppresses the malignant growth of human acute myeloid leukemia (AML) after successful engraftment in transgenic NSG-S xenograft mouse models of either established human AML cell line or primary AML cells. Daily treatment with fb-PMT (1–10 mg/kg body weight) subcutaneously (s.c.) for 3–4 weeks was associated with marked regression of leukemogenesis and extended survival in both models. The efficiency of the fb-PMT therapy was verified using in vivo imaging system (IVIS) imaging, flow cytometry, and histopathological examination to monitor the engraftment of leukemic cells in the bone marrow and other organs. fb-PMT therapy for 3–4 weeks at 3 and 10 mg/kg daily doses exhibited significant reduction (p < 0.0001) of leukemic cell burden of 74% and >95%, respectively. All fb-PMT-treated mice in the 10 mg/kg treatment arm successfully maintained remission after discontinuing the daily treatment. Comprehensive fb-PMT safety assessments demonstrated excellent safety and tolerability at multiple folds above the anticipated human therapeutic doses. Lastly, our genome-wide microarray screens demonstrated that fb-PMT works through the molecular interference mechanism with multiple signaling pathways contributing to growth and survival of leukemic cells.ConclusionOur preclinical findings of the potent anticancer activities of fb-PMT and its favorable safety profiles warrant its clinical investigation for the effective and safe management of AML.

Stepwise PEG synthesis featuring deprotection and coupling in one pot.

The stepwise synthesis of monodisperse polyethylene glycols (PEGs) and their derivatives usually involves using an acid-labile protecting group such as DMTr and coupling the two PEG moieties together under basic Williamson ether formation conditions. Using this approach, each elongation of PEG is achieved in three steps – deprotection, deprotonation and coupling – in two pots. Here, we report a more convenient approach for PEG synthesis featuring the use of a base-labile protecting group such as the phenethyl group. Using this approach, each elongation of PEG can be achieved in two steps – deprotection and coupling – in only one pot. The deprotonation step, and the isolation and purification of the intermediate product after deprotection using existing approaches are no longer needed when the one-pot approach is used. Because the stepwise PEG synthesis usually requires multiple PEG elongation cycles, the new PEG synthesis method is expected to significantly lower PEG synthesis cost.

Transferrin Receptor Targeted Polyplexes Completely Comprised of Sequence-Defined Components.

Human transferrin protein (Tf) modified polyplexes have already displayed encouraging potential for receptor-mediated nucleic acid delivery into tumors. The use of a blood-derived targeting protein and polydisperse macromolecular cationic subunits however presents a practical challenge for pharmaceutical grade production. Here, Tf receptor (TfR) targeted small interfering RNA (siRNA) polyplexes are designed that are completely composed of synthetic, monodisperse, and sequence-defined subunits generated by solid-phase supported synthesis. An optimized cationizable lipo-oligoaminoamide (lipo-OAA) is used for siRNA core polyplex formation, and a retro-enantio peptide (reTfR) attached via a monodisperse polyethylene glycol (PEG) spacer via click chemistry is applied for targeting. Improved gene silencing is demonstrated in TfR-expressing KB and DU145 cells. Analogous plasmid DNA (pDNA) polyplexes are successfully used for receptor-mediated gene delivery in TfR-rich K562 cells and Neuro2a cells. Six lipo-OAAs differing in their lipidic domain and redox-sensitive attachment of lipid residues are tested in order to evaluate the impact of core polyplex stability on receptor-dependent gene transfer.

Microfluidic Chip Device for In Situ Mixing and Fabrication of Hydrogel Microspheres via Michael-Type Addition.

Hydrogel microspheres are sought for a variety of biomedical applications, including therapeutic and cellular delivery, sensors, and lubricants. Robust fabrication of hydrogel microspheres with uniform sizes and properties can be achieved using microfluidic systems that rely on droplet formation and subsequent gelation to form microspheres. Such systems work well when gelation is initiated after droplet formation but are not practical for timed gelation systems where gelation is initiated prior to droplet formation; premature gelation can lead to device blockage, variable microsphere diameter due to viscosity changes in the precursor solution, and limited numbers of microspheres produced in a single run. To enable microfluidic fabrication of microspheres from timed gelation hydrogel systems, an in situ mixing region is needed so that various hydrogel precursor components can be added separately. Here, we designed and evaluated three mixing devices for their effectiveness at mixing hydrogel precursor solutions prior to droplet formation and subsequent gelation. The serpentine geometry was found to be the most effective and was further improved with the inclusion of a pillar array to increase agitation. The optimized device was shown to fully mix precursor solutions and enable the fabrication of monodisperse polyethylene glycol microspheres, offering great potential for use with timed gelation hydrogel systems.

Anhydrous Proton Transport within Phosphonic Acid Layers in Monodisperse Telechelic Polyethylenes

Polymers bearing phosphonic acid groups have been proposed as anhydrous proton-conducting membranes at elevated operating temperatures for applications in fuel cells. However, the synthesis of phosphonated polymers and the control over the nanostructure of such polymers is challenging. Here, we report the straightforward synthesis of phosphonic acid-terminated, long-chain aliphatic materials with precisely 26 and 48 carbon atoms (C26PA2 and C48PA2). These materials combine the structuring ability of monodisperse polyethylenes with the ability of phosphonic acid groups to form strong hydrogen-bonding networks. Anhydride formation is absent so that charge carrier loss by a condensation reaction is avoided even at elevated temperatures. Below the melting temperature (Tm), both materials exhibit a crystalline polyethylene backbone and a layered morphology with planar phosphonic acid aggregates separated by 29 and 55 Å for C26PA2 and C48PA2, respectively. Above Tm, the amorphous polyethylene (PE) segments coexist with the layered aggregates. This phenomenon is especially pronounced for the C26PA2 and is identified as a thermotropic smectic liquid crystalline phase. Under these conditions, an extraordinarily high correlation length (940 Å) along the layer normal is observed, demonstrating the strength of the hydrogen bond network formed by the phosphonic acid groups. The proton conductivity in both materials in the absence of water reaches 10-4 S/cm at 150 °C. These new precise phosphonic acid-based materials illustrate the importance of controlling the chemistry to form self-assembled nanoscale aggregates that facilitate rapid proton conductivity.

Research on Gliding and Discharge Performance of Suspended Injection from Syringe —Effect of Diameter Ratio of Suspending Particle against Needle Hole on Needle Passageability—

Suspended injectable formulations such as sustained-release luteinizing hormone-releasing hormone (LH-RH) analogue loaded in polylactic acid-glycolic acid copolymer (PLGA) particles have been developed on market. Such formulations have potential issue of suspended particles blocking the injection needle. In this research, two types of injectability tests (gliding force, particles discharge) were developed to evaluate the needle passageability of suspended particles. The model suspension was newly designed using mono-dispersed polyethylene (PE) spheres and qualified dispersing fluid to enhance universality and validity of the test. The suspension-filled syringe, in which three sizes of spheres (L, M, S) were dispersed, was vertically fixed and pushed by auto-compression/tensile tester. The gliding force was continuously detected during testing time and all discharged PE spheres were collected and weighed. The combination of sphere (L, M, S) and injection needle were varied to evaluate the effect of the diameter ratio of sphere against needle hole (D/W) on passageability through needle. These injectability tests revealed that the blockage of a needle hole was occasionally observed when the D/W value increased up to 0.35-0.5, which was detected by jump-up of gliding force and drastic decrease of discharged sphere. In addition, the effect of the formulation properties (concentration of suspended spheres, viscosity of dispersing fluid) and operational factor (injection speed) on injectability was also investigated. The results from this study would be valuable in developing suspended injections and predicting injection trouble at the medical scene.

Peptidic Monodisperse PEG "Comb" as Multifunctional "Add-On" Module for Imaging-Traceable and Thermo-Responsive Theranostics.

Monodisperse polyethylene glycols-modified (M-PEGylated) biomaterials exhibit high structural accuracy, biocompatibility, and fine-tunable physicochemical properties. To develop "smart" drug delivery systems in a controllable and convenient manner, a peptidic M-PEG "comb" with fluorinated L-lysine side chains and a fluorescent N-terminal is conveniently prepared as a 19 F magnetic resonance imaging (19 F MRI) and fluorescence dual-imaging traceable and thermo-responsive "add-on" module for liposomal theranostics in cancer therapy. The peptidic M-PEG "comb" has high biocompatibility, thermo-responsivity with a sharp lower critical solution temperature, an aggregation-induced emission fluorescence, and high 19 F MRI sensitivity. As a highly branched amphiphile, it self-assembles and firmly anchors on the doxorubicin-loaded liposomal nanoparticles, which M-PEGylates the liposomes and facilitates the thermo-responsive drug release and drug tracking with dual-imaging technologies. In a rodent xenograft model of human liver cancer HepG2 cells, the M-PEGylated liposomes exhibit long in vivo half time, low toxicity, high tumor accumulation, "hot spot" 19 F MRI, and therapeutic efficacy. With accurately programmable chemical structure, fine-tunable physicochemical and biological properties to meet the demands of diagnosis, drug delivery, and therapy, the M-PEG "comb" is promising as a versatile "add-on" module for rapid and convenient formulation of various "smart" theranostics.

Monodisperse and Telechelic Polyethylenes Form Extended Chain Crystals with Ionic Layers

We report the synthesis of ionic telechelic low-molecular-weight polyethylenes (PEs) with precise chain lengths that are derived from plant oils along with their morphologies and temperature-dependent ionic conductivities. Starting from the C48 telechelic dimethyl ester, or the C23 analogue for comparison, different ionic carboxylate end groups (H+, Na+, Cs+, Zn2+) were introduced by microwave-assisted saponification chemistry. Because of the precise length of the polymethylene sequence, these difunctional telechelic PEs crystallize into exceptionally well-ordered nanoscale-layered structures at room temperature. As a consequence of their extended chain crystal nature, the layer thickness is directly encoded by the telechelic molecules methylene chain length. Notably, C21(COONa)2, C46(COONa)2, and C46(COOCs)2 exhibit transitions in the crystalline structure prior to the fully disordered melt state, as evidenced by differential scanning calorimetry and in situ X-ray scattering. The melting transition is typically accompanied by a transition from layered ionic nanoaggregates between the crystallites to disordered ionic aggregates, with an interesting exception wherein the ionic layers transform to hexagonal symmetry. The temperature-dependent ionic conductivities of layered crystalline morphologies in the C48 materials exhibit an Arrhenius-like behavior, indicating a decoupling from the slower polymer segmental motions at T < Tm. These new precise ionic telechelic PEs produce well-defined nanoscale-layered morphologies with tunable ion transport properties that could be further developed as solid-state electrolytes.

Interaction of ultrasound with microporous polyethylene scaffolds

Ultrasound – stimulated healing in porous scaffolds has generated much interest in recent years. Most of the studies attempting to uncover the mechanisms behind this process, however, have mainly focused on the biochemical aspects and neglected the mechanical interaction between the ultrasonic waves and porous scaffolds. Such interactions are important, as they determine the distribution of ultrasonic waves around and within the scaffolds, which affects the local physical environment that, in turn, stimulates the biological responses. Here, we aim to identify the physical mechanism behind this interaction and elucidate the factors involved. To achieve this, microporous scaffolds were first fabricated by sintering monodisperse polyethylene (PE) colloids of different sizes. The transmission and reflection coefficients of these scaffolds were experimentally determined in an immersion setup, over the clinically relevant range of 1 – 30 MHz and compared with trends obtained from an analytical model and finite element simulations. The experimental and simulation data were found to agree well with the analytical solutions of Mie scattering, and the absorption coefficient was observed to depend more strongly on particle size than the exact shape or arrangement of the individual particles. Nonlinear fluctuations of the absorption coefficient with frequency were also predicted by the analytical model and observed experimentally. Furthermore, finite element simulations showed that the ultrasonic waves have poor penetration depth and scattering takes place mainly at the surface of the microporous scaffolds. Our results indicate that lower frequencies, smaller scaffold characteristic lengths, thinner scaffolds and orientations that maximize surface exposure of scaffolds to ultrasonic waves will enhance the penetration of ultrasound into the structures and potentially improve the rate of ultrasound-stimulated healing processes.