Polyethylene Glycol Chains Research Articles

Mitigation strategy of organic redox mediator crossover in chemically regenerative redox fuel cells

A modified (2, 2, 6, 6-tetramethylpiperidin-1-yl) oxyl (TEMPO) was developed for use as an organic mediator in chemically regenerative redox fuel cells (CRRFC). The main challenge of CRRFC is to determine the optimal redox molecule in terms of redox potential, stability, and fast regeneration kinetics. In order to avoid crossover of the TEMPO-based organic mediator through the membrane, the electroactive specie was functionalized with polyethylene glycol (PEG) chains of different lengths and the electrochemical properties of the synthesized species were assessed. Such chemical modification prevents the crossover of the redox mediators through the membrane, as demonstrated by ex situ analytical electrochemistry. The developed fuel cell provided a maximum power density of 110 mW cm−2 (150 mA cm−2 at 0.6 V) with TEMPO-based mediators bearing PEG chains, while exhibiting a higher stability than a cell using a commercial reference mediator. This study opens the route to design and select new organic mediators for applications in CRRFC and further improvements to enhance their stability over time.

Bottlebrush Polyethylene Glycol Nanocarriers Translocate across Human Airway Epithelium via Molecular Architecture-Enhanced Endocytosis.

Pulmonary drug delivery is critical for the treatment of respiratory diseases. However, the human airway surface presents multiple barriers to efficient drug delivery. Here, we report a bottlebrush poly(ethylene glycol) (PEG-BB) nanocarrier that can translocate across all barriers within the human airway surface. Guided by a molecular theory, we design a PEG-BB molecule consisting of a linear backbone densely grafted by many (∼1000) low molecular weight (∼1000 g/mol) polyethylene glycol (PEG) chains; this results in a highly anisotropic, wormlike nanocarrier featuring a contour length of ∼250 nm, a cross-section of ∼20 nm, and a hydrodynamic diameter of ∼40 nm. Using the classic air-liquid-interface culture system to recapitulate essential biological features of the human airway surface, we show that PEG-BB rapidly penetrates through endogenous airway mucus and periciliary brush layer (mesh size of 20-40 nm) to be internalized by cells across the whole epithelium. By quantifying the cellular uptake of polymeric carriers of various molecular architectures and manipulating cell proliferation and endocytosis pathways, we show that the translocation of PEG-BB across the epithelium is driven by bottlebrush architecture-enhanced endocytosis. Our results demonstrate that large, wormlike bottlebrush PEG polymers, if properly designed, can be used as a carrier for pulmonary and mucosal drug delivery.

PEGylated Micro/Nanoparticles Based on Biodegradable Poly(Ester Amides): Preparation and Study of the Core-Shell Structure by Synchrotron Radiation-Based FTIR Microspectroscopy and Electron Microscopy.

Surface modification of drug-loaded particles with polyethylene glycol (PEG) chains is a powerful tool that promotes better transport of therapeutic agents, provides stability, and avoids their detection by the immune system. In this study, we used a new approach to synthesize a biodegradable poly(ester amide) (PEA) and PEGylating surfactant. These were employed to fabricate micro/nanoparticles with a core-shell structure. Nanoparticle (NP)-protein interactions and self-assembling were subsequently studied by synchrotron radiation-based FTIR microspectroscopy (SR-FTIRM) and transmission electron microscopy (TEM) techniques. The core-shell structure was identified using IR absorption bands of characteristic chemical groups. Specifically, the stretching absorption band of the secondary amino group (3300 cm-1) allowed us to identify the poly(ester amide) core, while the band at 1105 cm-1 (C-O-C vibration) was useful to demonstrate the shell structure based on PEG chains. By integration of absorption bands, a 2D intensity map of the particle was built to show a core-shell structure, which was further supported by TEM images.

Study of ELU001, a C’Dot drug conjugate (CDC) targeting folate receptor α (FRα) overexpressing solid tumors.

TPS3173 Background: ELU001, pasifolate exatecan, is an ultra-small nanoparticle drug conjugate, known as a CDC (~6 nm), designed to target and penetrate into solid tumors. Due to its size, ELU001 exhibits rapid renal elimination which is expected to reduce or eliminate the toxicities associated with many antibody drug conjugates. ELU001 has ~13 folic acid targeting moieties and ~21 cathepsin-B cleavable exatecan topoisomerase-1 inhibitor payloads covalently bound to short polyethylene glycol chains surrounding a silica core, the C’Dot. ELU001 binds to cancer cells expressing FRα and is internalized into the lysosome where it releases the exatecan payload. ELU001’s dose escalation study reported at ESMO Congress 2023 (1), examined weekly, bi-weekly (Q2W), and tri-weekly schedules over a range of doses in 42 patients. The study revealed that ELU001 could be administered safely and identified a dose level and schedule for the Expansion Studies described below. 22 of the patients with ovarian or endometrial cancers had >1 post-baseline scan(s), of these 2 had a PR and 19 had SD by RECIST v1.1 criteria. ELU001 demonstrated activity against tumors across a range of FRα expression levels, from low to high, retrospectively assessed using the VENTANA FOLR1 RxDx assay and the PS2+ scoring system. Methods: The current multicenter, Tumor Group Expansion open-label phase 1/2 clinical trial investigates ELU001 in patients with ovarian and endometrial cancers and is enrolling three cohorts; 1) ovarian cancer with high FRα expression, 2) ovarian cancer with moderate and low expression and 3) endometrial cancer with low to high expression with assessments based upon the PS2+ scoring system (high = ≥ 75%, moderate = ≥ 50% to < 75%, low = 25% to < 50%, negative = <25% of tumor cells with 2+ or 3+ staining intensity). An initial exploratory dose of 2.0 mg/m2 Q2W was employed in all three cohorts and a second dose of 1.7 mg/m2 Q2W will be studied in the ovarian cancer cohorts. Patients will ultimately be randomized to one of two or more doses to optimize dosing for registration. Primary endpoint: Objective Response Rate (ORR); secondary endpoints include DOR, PFS, TFST, PFS2, OS, adverse events, PK, and ADA assessments. Approximately 20 patients per tumor group will be recruited in the U.S. 1. Ann. Oncol. (2023) 34 (suppl_2): S458-S497. Clinical trial information: NCT05001282 .

Understanding Na+ Diffusion, Physicochemical Behavior, and Electrochemical Performance of a Gel Polymer Electrolyte.

Gel polymer electrolytes (GPEs) represent a credible alternative to organic liquid electrolytes (LEs) for safer sodium metal batteries. As a compromise between solid polymer electrolytes and LEs, GPEs ensure a good ionic conductivity, improve the electrolyte/electrode interface, and prevent solvent leaks. Herein, a GPE based on acrylate-bifunctionalized polyethylene glycol chains mixed with an ether solvent (TEGDME) and a polyethylene glycol diacrylate (PEG600DA) in a 50/50 wt % ratio was prepared by ultraviolet photopolymerization. Sodium bis(fluorosulfonyl)imide salt (NaFSI) was added at different concentrations to study its interactions with the solvent and/or the cross-linked polymer. Infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and swelling ratio characterizations were combined to determine the physicochemical properties of the GPE. Complementary characterizations including electrochemical impedance spectroscopy, chronopotentiometry, and cyclic voltammetry allowed correlating the physicochemical properties of the GPE to its electrochemical performance. Then, improvements were obtained by careful combination of its components. The cross-linking agent allowed us to obtain a polymer matrix that traps the organic solvent and prevents leakage. Such a solvent inclusion reduces the rigidity of the membrane and lowers its viscosity, offering a room temperature ionic conductivity of 4.8 × 10-4 Ω-1 cm-1. The control of polymer's tortuosity leads to a stable cycling vs sodium metal over several hundred hours without increase of the polarization. Finally, optimization of the salt loading plays a major role in electrostatic cross-linking, leading to an improvement of the mechanical properties of the GPE without reducing its conductivity.

Sol-gel synthesized porous Yb-K2Ti6O13(n) for photocatalytic degradation of azophloxine: effect of polyethylene glycol chain length

Sol-gel synthesized porous Yb-K2Ti6O13(n) for photocatalytic degradation of azophloxine: effect of polyethylene glycol chain length

Synthesis of polyethylene glycol-grafted magnetic nanoparticles for the fast and efficient extraction of anabolic substances from human urine

Anabolic steroids and β-agonists are commonly prohibited substances found in doping control studies; therefore, the determination of anabolic substances in biological samples is crucial. To analyze the anabolic compounds in urine, an adsorbent, polyethylene glycol (PEG)-grafted magnetic nanoparticle material (Fe3O4@SiO2-PEG), with low toxicity and strong biocompatibility was prepared in this investigation. Compared to those of Fe3O4 and Fe3O4@SiO2, the grafted PEG chains (approximately 5.4 wt.%) on the magnetic nanoparticles improved the extraction efficiencies by factors of 3.9–17.0 and 2.5–2.9, respectively, likely due to the electrostatic attraction and hydrogen bonding. To achieve maximum extraction efficiency, several extraction parameters were optimized, including the kind and volume of desorption solvent, pH, and the extraction and desorption time. The standard curves were linear within the range of 0.5–20 μg/L for methyltestosterone and trenbolone, and 0.02–5 μg/L for clenbuterol. The limits of detection for the three drugs were 0.01–0.12 μg/L. The limits of quantification were 0.02–0.40 μg/L. The levels of precision of the optimized method were assessed based on the respective intra- and inter-day and batch-to-batch relative standard deviations in the ranges of 3.2–5.2 % (n = 5), 5.9–11.3 % (n = 4), and 6.7–9.2 % (n = 3). The Fe3O4@SiO2-PEG nanoparticles could exclude urine matrix interferences (matrix effect of 91.8–98.1 %) and achieve satisfactory recoveries (75.5–116.1 %), affording sensitive and accurate determination of trace anabolic substances in urine.

Polyetheretherketone fiber-supported polyethylene glycols for phase-transfer catalysis in its surface layer

Cleaner and more efficient catalytic processes are becoming more relevant to the synthetic chemistry for reducing wastes. And herein, a commercially available ultra-high strength textile fiber polyetheretherketone (PEEK) was directionally modified by post-functionalization procedure to graft polyethylene glycols (PEG) into its surface layer to form a hydrophilic interface, and the resulted PEEK-PEG materials capable of acting as the supported phase-transfer catalysts for sorts of organic conversions in a cleaner manner were reported. The fiber samples generated during the preparation and utilization processes were observed and characterized in detail by various techniques such as morphology, mechanical properties, elemental analysis, FTIR spectroscopy and X-ray diffraction and TG analysis, and rest assured that the strategy was dependable. Moreover, the phase-transfer catalytic performance of the fiber-supported catalyst PEEK-PEG was verified in different kinds of substitution reactions, and the effects of PEG type, PEG loading and the correspondingly reaction conditions on the phase-transfer catalytic system were inspected meticulously, which were further conducive to sustain the proposed phase-transfer catalytic mechanism, and with the synergistic effect of the fiber support and PEG chain in the hydrophilic interface to afford the substitutions proceeded smoothly to obtain good to excellent product yields. Additionally, the fiber catalyst could be recycled simply and reused over 15 cycles with excellent stability under the strong caustic condition, and the catalytic system could be enlarged to the gram-scale in a spinning basket reactor, to provide a cleaner manner for phase-transfer catalysis in organic conversions with the potential of industrial application.

Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Adsorption and Structuration of PEG Thin Films: Influence of the Substrate Chemistry.

This study investigates polyethylene glycol (PEG) homopolymer thin film adsorption on gold surfaces of controlled surface chemistry. The conformational states of physisorbed PEG are analyzed through polarization modulation infrared reflection-absorption spectrometry (PM-IRRAS). The PM-IRRAS principle is based on specific optical selection rules allowing the detection of surface-specific FTIR response of thin polymer films on the basis of differential reflectivity at the polymer/substrate interface for p- and s-polarized light. The intensification of the electric field generated at the PEG/substrate interface for p-polarized IR light in comparison with s-polarized light permits the analysis of PEG chain anisotropy and conformational changes induced by the adsorption. Results showed that PEG adsorbs on model substrates having a rather hydrophilic character in a way that the PEG chains spread parallel to the surface. In the case of a very hydrophilic substrate, the adsorbed PEG chains are in a stable thermodynamic state which allows them to arrange and crystallize as stacked crystalline lamellae after adsorption. The surface topography and morphology of the PEG thin films were also investigated by atomic force microscopy (AFM). While in the bulk state, PEG crystallizes in the form of large spherulites; on substrates whose adsorption is favored by surface chemistry, PEG crystallizes in the form of stacked lamellae with a thickness equal to 20 nm. Conversely, on a hydrophobic substrate, the PEG chains do not crystallize and adsorption occurs in the statistical coil state.

Tuning physicomechanical properties of PEG-interpenetrated anionically modified semi-IPN cryogels functionalized with carboxylate groups

Anionically modified interpenetrated polymer network (semi-IPN) cryogels containing linear polyethylene glycol chains (PEG) were prepared via in situ synthesis and directed assembly of the negatively charged copolymer poly(acrylamide-co-sodium acrylate) (PAN) network template. The influence of reaction conditions; the concentration of linear PEG chains, and polymerization temperature on the elasticity and swelling of these IPNs was analyzed in detail. The interpenetrating structure of PEG chains and PAN host network have been confirmed by FTIR, TGA and XRD analysis. The equilibrium water content, oscillatory swelling/deswelling kinetics, and water transport mechanism were analyzed as a function of PEG content. The results showed that semi-IPN gels exhibited different swelling behavior as the reaction conditions varied. Addition of 13.9% (w/v) PEG resulted in a 25-fold increase in the swelling ratio of semi-IPN hydrogels. By performing compression tests on semi-IPN gels to determine the change of compression properties, the effective cross-linking density of semi-IPN PAN/PEG was expressed as a second-order polynomial depending on the amount of PEG. The swollen modulus of semi-IPN cryogels was much higher than that of semi-IPN hydrogels for all PEG concentrations. Semi-IPNs showed reversible on-off switching with remarkable sensitivity to external pH stimulus. Structural parameters, degree of swelling, volume fraction of cross-linked polymer in the swollen state, and diffusion coefficients due to pH-induced swelling of semi-IPN gels were determined. The presence of linear PEG chains in the structure promoted swelling by both increasing the swelling rate and significantly reducing the time required to reach the equilibrium-state. The swelling process was Fickian diffusion, and the diffusion coefficients for swelling of PEG-interpenetrated semi-IPNs increased with PEG content. The effectiveness of removing methylene blue (MB) dye from aqueous solutions by semi-IPNs was evaluated. Batch adsorption experiments were performed as a function of the gelation temperature, amount of PEG, contact time, and initial dye concentration. The adsorption isotherm and kinetics were described well by Langmuir isotherm model and pseudo-second-order model, respectively. Adsorption of MB was a multi-step process involving surface adsorption followed by intra-particle diffusion. Semi-IPN PAN/PEG cryogels prepared under cryocondition with high adsorption capacities and fast adsorption rates have been developed as new adsorbents effective in removing dyes and other toxic substances with higher mechanical strength in water and wastewater treatment.

Polymer coating for antiicing and deicing

Ice accretion may cause serious safety risk and huge economic loss for outdoor facilities. Herein, we report a waterborne polymeric coating based on a copolymer network of methacrylic acid (MAA), acrylamide (AM), N-2-hydroxyethyl acrylamide (HEAA), and methoxypolyethylene glycol (MPEG) with free polyethylene glycol (PEG) dispersed in it. Owing to the good compatibility of free PEG chains and the PEG side chains of the copolymer, the hydrogen bonding between acrylic copolymer and PEG, the free PEG chains can well be trapped in the network with some segments out of the mesh as short PEG chains are grafted on the coating surface, so that the surface has liquid-like properties. Water droplets can readily slip off on the coating surface with a small sliding angle (<30°). Particularly, the surface can hold the properties for a long duration upon water flushing, cycle of wetting-drying, and salt spraying tests. The polymer coating can find application in icing prevention and removal.

Homo-Dyad with Outer Hydration Layer Approach for Developing NIR-II Chromophore of High Stability and Water-Solubility as Injectable and Sprayable Optical Probe.

Dyes with extended conjugate structures are the focus of extensive design and synthesis efforts, aiming to confer unique and improved optical and electronic properties. Such advancements render these dyes applicable across a wide spectrum of uses, ranging from second-window near-infrared (NIR-II) bioimaging to organic photovoltaics. Nevertheless, the inherent benefits of long conjugation are often accompanied by persistent challenges like aggregation, fluorescence quenching, absorption blueshift, and low stability and poor water solubility. Herein, a unique structural design strategy termed "homo-dyad with outer hydration layer" is introduced to address these inherent problems, tailored for the development of imaging probes exhibiting long absorption/emission wavelengths. This approach involves bringing two heptamethine cyanines together through a flexible linker, forming a homo-dyad structure, while strategically attaching four polyethylene glycol (PEG9) chains to the terminal heterocycles. This approach imparts excellent water solubility, biocompatibility, and enhanced chemical, photo-, and spectral stability for the dyes. Utilizing this strategy, a biomarker-activatable probe (HD-FL-4PEG9-N) for NIR-II fluorescent and 3D multispectral optoacoustic tomography imaging is developed, and its effectiveness in disease visualization. It can not only serve as an injectable probe for acute kidney injury imaging due to its high water solubility, but also a sprayable probe for imaging bacterial-infected wounds.

Water-Soluble Molecular Cages for Biological Applications.

The field of molecular cages has attracted increasing interest in relation to the development of biological applications, as evidenced by the remarkable examples published in recent years. Two key factors have contributed to this achievement: First, the remarkable and adjustable host-guest chemical properties of molecular cages make them highly suitable for biological applications. This allows encapsulating therapeutic molecules to improve their properties. Second, significant advances have been made in synthetic methods to create water-soluble molecular cages. Achieving the necessary water solubility is a significant challenge, which in most cases requires specific chemical groups to overcome the inherent hydrophobic nature of the molecular cages which feature the organic components of the cage. This can be achieved by either incorporating water-solubilizing groups with negative/positive charges, polyethylene glycol chains, etc.; or by introducing charges directly into the cage structure itself. These synthetic strategies allow preparing water-soluble molecular cages for diverse biological applications, including cages' anticancer activity, anticancer drug delivery, photodynamic therapy, and molecular recognition of biological molecules. In the review we describe selected examples that show the main concepts to achieve water solubility in molecular cages and some selected recent biological applications.

Shell‐sheddable and charge switchable magnetic nanoparticle as pH‐sensitive nanocarrier for targeted drug delivery applications

AbstractA pH‐sensitive shell‐sheddable magnetic nanocarrier was prepared based on Fe3O4@SiO2 nanoparticles coated with polyethyleneimine (PEI) and polyethyleneglycol (PEG). The PEI was coated on Fe3O4@SiO2 nanoparticles through an electrostatic attraction and the PEG chains were connected to the PEI via pH‐sensitive benzoic‐imine bonds. The synthesized products and final nanocarrier were characterized with FT‐IR, 1H NMR, dynamic light scattering (DLS), zeta‐potential, TEM, and vibrating‐sample magnetometer (VSM). The PEI, as a middle layer, was used to load the curcumin (an anticancer drug) via van der Waals interactions and the shedding of PEG as a hydrophilic corona at the tumor pH (acidic) could induce the release of the drug. The curcumin loading content was found to be ~15% and curcumin‐loaded magnetic nanoparticles (C‐LMNs) showed more triggered release at the tumor pH (5.6) than physiological pH (7.4). In comparison to pure magnetic nanoparticles (MNs), the C‐LMNs showed more cytotoxicity to human prostate cancer cell (PC‐3) and also resulted in an increased rate of late apoptotic/necrotic PC‐3 cells, assessed by flow cytometry analysis. In conclusion, the C‐LMN as pH‐ and magnetic responsive nanocarrier showed good potential for targeted curcumin delivery in therapy of prostate cancer.

Polyethylene Glycol Cross-Linked Hydrogel for Drug Absorption Properties

ABSTRACT Three-dimensional polymeric networks called hydrogels have drawn a lot of interest in a variety of biomedical applications because of their distinctive qualities, like high water content and biocompatibility. Hydrogels can be strengthened mechanically and become more stable via cross-linking. In this study, we described the synthesis and characterization of a cross-linked hydrogel made of polyethylene glycol (PEG) capable of absorbing drug. The hydrogel was created by using a polymerization procedure to cross-link PEG chains. In order to allay this worry, we added particular functional groups to the hydrogel matrix that had a strong affinity for glutaraldehyde. These functional groups made it easier for excess glutaraldehyde to be absorbed and sequestered inside the hydrogel, lowering its cytotoxic potential. After incubation with the hydrogel, the residual glutaraldehyde concentration in solution was measured in order to assess the glutaraldehyde absorption potential.

Abstract 7173: Animal pharmacokinetics of an anti-Her2+ immunoliposome of docetaxel

Abstract Despite the success of docetaxel in combination with trastuzumab in HER2+ breast cancer, docetaxel still has serious limitations, including poor water solubility and the canonical systemic toxicity of taxanes. These side effects of taxanes need to be overcome to improve patient management. In this context, we have developed a nanoparticle drug delivery system. We have developed an immunoliposome loaded with docetaxel and grafted with trastuzumab using a microfluidic method by mixing an aqueous phase (KH2PO4 buffer) and an organic phase composed of phosphatidylcholine, cholesterol and PEGmal in a molar ratio of 50:31:1, to which docetaxel is added at a rate of 1.8% of the total lipid. We perform a thiolation reaction to graft the trastuzumab onto the polyethylene glycol chain. Resulting immunoliposomes were characterized by a mean diameter of 140 nm, a docetaxel encapsulation rate of 73% and a trastuzumab uptake rate of 400 units of trastuzumab by nanoparticle. C57BL/6 mice were administered with docetaxel 1.9 mg/kg and trastuzumab 160 ng/kg or a mixture of free drugs or as liposomes at the same dose by intraperitoneal injection. Blood was collected 1h, 2h, 3h, 6h, 8h and 24h after injection and plasma was analyzed by HPLC-UV with Paclitaxel as internal standard. For each treatment group, pharmacokinetic parameters and exposure metrics were calculated using PKanalix®: half-life T1/2, elimination rate constant Kel and area under the curve AUC at the end points (AUCtlast) and infinity (AUCinfinity). Statistical tests were performed with Sigmastats®. The results showed a marked change in pharmacokinetics with increased plasma exposure with liposomal docetaxel. Preliminary results show a longer half-life for liposomal docetaxel (40.76 h VS. 4.33 h, i.e., a 9.4-fold increase). The concentration of docetaxel appeared to decrease more rapidly between T1h and T6h with free docetaxel (Kel 0.16h-1) than with liposomal docetaxel (Kel 0.017h-1). The concentration of docetaxel reached a plateau over time, up to 24 hours (52.72± 9.45 ng/ml) in mice treated with immunoliposomes whereas Docetaxel was undetectable at T24h when treated with free drugs. There was a statistical difference in PK at T6h between liposomal docetaxel and free docetaxel, 69.86 ± 15.25 ng/ml and 53.67 ± 4.92 ng/ml, respectively (p &amp;lt; 0.001, non-paired t-test). Liposomal docetaxel showed higher AUC0-t (x3.75) and AUC0-∞ values (x5.9) compared to non-liposomal docetaxel. In conclusion, these preliminary results suggest that we have developed a promising immunoliposome for the systemic delivery of docetaxel in HER2+ breast cancer with sustained exposure. Citation Format: Mathilde Dacos, Erwan Diroff, Sarah Giacometti, Joseph Ciccolini, Raphaelle Fanciullino. Animal pharmacokinetics of an anti-Her2+ immunoliposome of docetaxel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7173.

Targeted Single Particle Tracking with Upconverting Nanoparticles.

Single particle tracking (SPT) is a powerful technique for real-time microscopic visualization of the movement of individual biomolecules within or on the surface of living cells. However, SPT often suffers from the suboptimal performance of the photon-emitting labels used to tag the biomolecules of interest. For example, fluorescent dyes have poor photostability, while quantum dots suffer from blinking that hampers track acquisition and interpretation. Upconverting nanoparticles (UCNPs) have recently emerged as a promising anti-Stokes luminescent label for SPT. In this work, we demonstrated targeted SPT using UCNPs. For this, we synthesized 30 nm diameter doped UCNPs and coated them with amphiphilic polymers decorated with polyethylene glycol chains to make them water-dispersible and minimize their nonspecific interactions with cells. Coated UCNPs highly homogeneous in brightness (as confirmed by a single particle investigation) were functionalized by immunoglobulin E (IgE) using a biotin-streptavidin strategy. Using these IgE-UCNP SPT labels, we tracked high-affinity IgE receptors (FcεRI) on the membrane of living RBL-2H3 mast cells at 37 °C in the presence and absence of antigen and obtained good agreement with the literature. Moreover, we used the FcεRI-IgE receptor-antibody system to directly compare the performance of UCNP-based SPT labels to organic dyes (AlexaFluor647) and quantum dots (QD655). Due to their photostability as well as their backgroundless and continuous luminescence, SPT trajectories obtained with UCNP labels are no longer limited by the photophysics of the label but only by the dynamics of the system and, in particular, the movement of the label out of the field of view and/or focal plane.

A Benchtop Round Window Model for Studying Magnetic Nanoparticle Transport to the Inner Ear.

The round window membrane (RWM) presents a significant barrier to the local application of therapeutics to the inner ear. We demonstrate a benchtop preclinical RWM model and evaluate superparamagnetic iron oxide nanoparticles (SPIONs) as vehicles for magnetically assisted drug delivery. Guinea pig RWM explants were inset into a 3D-printed dual chamber benchtop device. Custom-synthesized 7-nm iron core nanoparticles were modified with different polyethylene glycol chains to yield two sizes of SPIONs (NP-PEG600 and NP-PEG3000) and applied to the benchtop model with and without a magnetic field. Histologic analysis of the RWM was performed using transmission electron microscopy (TEM) and confocal microscopy. Over a 4-h period, 19.5 ± 1.9% of NP-PEG3000 and 14.6 ± 1.9% of NP-PEG600 were transported across the guinea pig RWM. The overall transport increased by 1.45× to 28.4 ± 5.8% and 21.0 ± 2.0%, respectively, when a magnetic field was applied. Paraformaldehyde fixation of the RWM decreased transport significantly (NP-PEG3000: 7.6 ± 1.5%; NP-PEG600: 7.0 ± 1.6%). Confocal and electron microscopy analysis demonstrated nanoparticle localization throughout all cellular layers and layer-specific transport characteristics within RWM. The guinea pig RWM explant benchtop model allows for targeted and practical investigations of transmembrane transport in the development of nanoparticle drug delivery vehicles. The presence of a magnetic field increases SPION delivery by 45%-50% in a nanoparticle size- and cellular layer-dependent manner. NA Laryngoscope, 134:3355-3362, 2024.

Mechanical Stretch α-Cyclodextrin Pseudopolyrotaxane Elastomer with Reversible Phosphorescence Behavior.

Polyethylene glycol chains in two terminals of the naphthalene functional group are threaded into α-cyclodextrin cavities to form the pseudopolyrotaxane (NPR), which not only effectively induces the phosphorescence of the naphthalene functional group by the cyclodextrin macrocycle confinement, but also provides interfacial hydrogen bonding assembly function between polyhydroxy groups of cyclodextrin and waterborne polyurethane (WPU) chains to construct elastomers. The introduction of NPR endows the elastomer with enhanced mechanical properties and excellent room temperature phosphorescent(RTP) emission (phosphorescence remains in water, acid, alkali, and organic solvents, even at 160 °C high temperatures). Especially, the reversible mechanically responsive room temperature phosphorescence behavior (phosphorescence intensity increased three times under 200% strain) can be observed in the mechanical stretch and recover process, owing to strain-induced microstructural changes further inhibiting the non-radiative transition and the vibration of NPR. Therefore, changing the phosphorescence behavior of supramolecular elastomers through mechanical stretching provides a new approach for supramolecular luminescent materials.