Phospholipid Polymer Research Articles

Stent coating containing a charged silane coupling agent that regulates protein adsorption to confer antithrombotic and cell-adhesion properties

The evolution of endovascular therapies, particularly in the field of intracranial aneurysm treatment, has been truly remarkable and is characterized by the development of various stents. However, ischemic complications related to thrombosis or downstream emboli pose a challenge for the broader clinical application of such stents. Despite advancements in surface modification technologies, an ideal coating that fulfills all the desired requirements, including anti-thrombogenicity and swift endothelialization, has not been available. To address these issues, we investigated a new coating comprising 3-aminopropyltriethoxysilane (APTES) with both anti-thrombogenic and cell-adhesion properties. We assessed the anti-thrombogenic property of the coating using an in vitro blood loop model by evaluating the platelet count and the level of the thrombin–antithrombin (TAT) complex, and investigating thrombus formation on the surface using scanning electron microscopy (SEM). We then assessed endothelial cell adhesion on the metal surfaces. In vitro blood tests revealed that, compared to a bare stent, the coating significantly inhibited platelet reduction and thrombus formation; more human serum albumin spontaneously adhered to the coated surface to block thrombogenic activation in the blood. Cell adhesion tests also indicated a significant increase in the number of cells adhering to the APTES-coated surfaces compared to the numbers adhering to either the bare stent or the stent coated with an anti-fouling phospholipid polymer. Finally, we performed an in vivo safety test by implanting coated stents into the internal thoracic arteries and ascending pharyngeal arteries of minipigs, and subsequently assessing the health status and vessel patency of the arteries by angiography over the course of 1 week. We found that there were no adverse effects on the pigs and the vascular lumens of their vessels were well maintained in the group with APTES-coated stents. Therefore, our new coating exhibited both high anti-thrombogenicity and cell-adhesion properties, which fulfill the requirements of an implantable stent.

Biomimetic nanotherapeutics for homotypic-targeting photothermal/chemotherapy of oral cancer

Given the inherent complexity of cancer treatment and the limitations of singular therapeutic modalities, the development of an optimal nanocarrier system capable of facilitating synergistic organic therapy remains a profound challenge. Herein, a synergetic chemo/photothermal therapy nanoplatform was exploited to specifically tailor for the augmented treatment of oral cancer. A cancer cell membrane-camouflaged nanocarrier was developed with a polymeric core encapsulating doxorubicin (DOX). The designed nanoparticles (CC@DOXNPs) inherited the functional membrane proteins from the source cancer cells, endowing their remarkable ability to selectively target cancer cells delivery both in vitro and in vivo. Moreover, indocyanine green (ICG), modified with the phospholipid polymer DSPE-PEG2000, was introduced into the cancer cell membrane to enable photothermal therapy. Remarkably, as evaluated in a preclinical subcutaneous and orthotopic mice model of oral cancer, biomimetic composite nanotherapeutics (lip-CC@DOXNPs) could significantly accumulate into tumor lesion and effectively suppress tumor growth under the near-infrared (NIR, 808 nm) irradiation, without causing the undesirable systematic toxicity. Moreover, RNA sequence analyses indicated that chemo/photothermal therapy triggers the intrinsic mitochondria-mediated apoptosis through the p53 signaling pathway. Combined with gene expression results, this intrinsic mitochondria-mediated apoptosis pathway was further demonstrated. Collectively, this multifaceted nanoplatforms possess a remarkable capability for tumor-targeting drug delivery, and the proficient photothermal conversion ability, rendering them an ideal therapeutic approach for oral cancer treatment.

Solubilization of Poorly Water-soluble Drugs with Amphiphilic Phospholipid Polymers

Most drug candidates developed in recent years are poorly water-soluble, which is a key challenge in pharmaceutical science. Various solubilization methods have been investigated thus far, most of which require solubilizers that provide a local hydrophobic environment wherein a drug can dissolve or induce interactions with drug molecules. We have focused on amphiphilic 2-methacryloyloxyethyl phosphoryl choline (MPC) polymers. In addition to the ease of molecular design of amphiphilic MPC polymers owing to their chemical structures, they have been reported to possess high biocompatibility in various biomaterial applications. Additionally, amphiphilic MPC polymers have been applied in the pharmaceutical field, especially in solubilization. We have qualitatively and quantitatively evaluated the effects of the chemical structure and physical properties of the solubilizer on the MPC polymers. In particular, MPC polymers with different chemical structures were designed and synthesized. The inner polarity and molecular mobility in the polymer aggregates were evaluated, indicating that the intrinsic properties reflect the chemical structure of the polymer. Additionally, amphiphilic MPC polymers were used to improve the solubility of poorly water-soluble drugs and as solid dispersion carriers, and they exhibited superior solubilizing abilities compared to a commonly used polymer. Furthermore, the solubility of biopharmaceuticals, such as peptides, was improved. It is possible to design and synthesize optimal structures based on the polarity of the hydrophobic environment and the intermolecular interaction with a drug. This research provides a unified interpretation of drugs and efficiently summarizes knowledge about drug development, which will facilitate the efficient and rapid development of drug formulations.

Effective magnetic hyperthermia induced by mitochondria-targeted nanoparticles modified with triphenylphosphonium-containing phospholipid polymers.

Magnetic hyperthermia (MHT) is a promising cancer treatment because tumor tissue can be specifically damaged by utilizing the heat generated by nano-heaters such as magnetite nanoparticles (MNPs) under an alternating magnetic field. MNPs are taken up by cancer cells, enabling intracellular MHT. Subcellular localization of MNPs can affect the efficiency of intracellular MHT. In this study, we attempted to improve the therapeutic efficacy of MHT by using mitochondria-targeting MNPs. Mitochondria-targeting MNPs were prepared by the modification of carboxyl phospholipid polymers containing triphenylphosphonium (TPP) moieties that accumulate in mitochondria. The mitochondrial localization of polymer-modified MNPs was supported by transmission electron microscopy observations of murine colon cancer CT26 cells treated with polymer-modified MNPs. In vitro and in vivo MHT using polymer-modified MNPs revealed that the therapeutic effects were enhanced by introducing TPP. Our results indicate the validity of mitochondria targeting in enhancing the therapeutic outcome of MHT. These findings will pave the way for developing a new strategy for the surface design of MNPs and therapeutic strategies for MHT.

Cellular Internalization and Exiting Behavior of Zwitterionic 4-Armed Star-Shaped Polymers.

The zwitterionic phospholipid polymer poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) is amphiphilic copolymer, and it has been reported to directly penetrate cell membranes and have good cytocompatibility. Conventional PMBs are linear-type random copolymers that are polymerized by a free radical polymerization technique. In contrast, star-shaped polymers, or simple branched-type polymers, have unique properties compared to the linear types, for example, a viscosity based on the effect of the excluded volume. In this study, a branched architecture was introduced into a PMB molecular structure, and a 4-armed star-shaped PMB (4armPMB) was synthesized by an atom transfer radical polymerization (ATRP) technique known as living radical polymerization. Linear-type PMB was also synthesized using ATRP. The effects of the polymer architecture on cytotoxicity and cellular uptake were investigated. Both 4armPMB and LinearPMB were successfully synthesized, and these polymers were verified to be water soluble. Pyrene fluorescence in the polymer solution indicated that the architecture had no effect on the behavior of the polymer aggregates. In addition, these polymers caused no cytotoxicity or cell membrane damage. The 4armPMB and LinearPMB penetrated into the cells after a short incubation period, with similar rates. In contrast, the 4armPMB showed a quicker back-diffusion from the cells than that of LinearPMB. The 4armPMB showed fast cellular internalization and exiting behaviors.

Targeting and sensitizing MDR cancer by an MMP2 and pH dual-responsive ZnO-based nanomedicine

Zinc oxide nanoparticles (ZnO NPs) have been known as a therapeutic agent and drug delivery system for treating various diseases, including infectious diseases and cancer. However, due to the low biocompatibility, short in vivo half-life, and potential toxicity, the previous studies on ZnO NPs were mainly focused on their in vitro applications. The effective and safe ZnO NP-based systems which can be used for in vivo drug delivery have been rarely reported. In this study, we developed a novel dual-responsive hybrid ZnO NP (ZnO/DPPG/PEG-pp-PE) consisting of the ZnO NPs, phospholipid (DPPG), and enzyme-sensitive amphiphilic polymer (PEG-pp-PE), which could respond to both tumoral matrix metalloproteinase 2 (MMP2) and intracellular acidic pH, for tumor-targeted drug delivery and multidrug resistant (MDR) cancer treatment. The dual-responsive ZnO/DPPG/PEG-pp-PE could easily load the model drug, doxorubicin (DOX), and showed excellent physicochemical properties, stability, and MMP2 and pH dual sensitivity. The ZnO/DPPG/PEG-pp-PE/DOX showed the MMP2-dependent cellular uptake, enhanced cell penetration, and improved anticancer activity in the MDR cancer cells and their spheroids. In the MDR tumor-bearing mice, the ZnO/DPPG/PEG-pp-PE/DOX improved the biocompatibility, tumor targetability, and anticancer activity of DOX and ZnO without significant toxicity compared to the free DOX, ZnO/DOX, and nonsensitive ZnO NPs. The data suggested that the dual-sensitive ZnO-based nanomedicine could be a promising delivery system for targeted drug delivery and therapy against the MDR cancer.

Ultra-High-Molecular-Weight Polyethylene in Hip and Knee Arthroplasties.

Ultra-high-molecular-weight polyethylene (UHMWPE) wear and particle-induced osteolysis contribute to the failure of total hip arthroplasty (THA) and total knee arthroplasty (TKA). Highly crosslinked polyethylene (HXLPE) was developed in the late 1990s to reduce wear and has shown lower wear rates and loosening than conventional UHMWPE in THA. The irradiation dose for crosslinking is up to 100 kGy. However, during crosslinking, free radical formation induces oxidation. Using HXLPE in THA, the cumulative revision rate was determined to be significantly lower (6.2%) than that with conventional UHMWPE (11.7%) at a mean follow-up of 16 years, according to the Australian Orthopaedic Association National Joint Replacement Registry. However, HXLPE does not confer to TKA the same advantages it confers to THA. Several alternatives have been developed to prevent the release of free radicals and improve polymer mechanical properties, such as thermal treatment, phospholipid polymer 2-methacryloyloxyethyl phosphorylcholine grafting, remelting, and vitamin E addition. Among these options, vitamin E addition has reported good clinical results and wear resistance similar to that of HXLPE without vitamin E, as shown by short-term clinical studies of THA and TKA. This review aims to provide a comprehensive overview of the development and performance of UHMWPE in THA and TKA.

A Solid–Liquid Composite Lubricating “Nano‐Snowboard” for Long‐Acting Treatment of Osteoarthritis

AbstractOsteoarthritis is a chronic inflammatory disease characterized by cartilage degeneration. Anti‐inflammatory therapy has limited effects, and effective reduction of cartilage wear through lubrication is essential. In vivo stability and lubricity of commercial lubricants are insufficient, leading to failure of lubricating treatment and progression of osteoarthritis. To address these issues, new therapeutic methods combining anti‐inflammation and stable high‐performance lubrication are developed. Inspired by the sliding mechanism of snowboards, a “nano‐snowboard” by modifying molybdenum disulfide (MoS2) with a biomimetic phospholipid polymer poly (dopamine methacrylamide‐co‐2‐methacryloyloxyethyl phosphorylcholine) (PDMPC) and loading anti‐inflammatory drug diclofenac sodium (DS), namely MoS2‐PDMPC‐DS, has been synthesized. MoS2 with a 2D layered structure and photothermal properties, serves as solid lubricant and drug carrier. Meanwhile, the modification of PDMPC on the surface of MOS2 avoids the oxidative denaturation of MoS2 in a physiological environment, forming solid–liquid composite lubrication and improving the lubricity and stability of MoS2 in the joint cavity. In vitro and in vivo experiments show that MoS2‐PDMPC‐DS can stay in the joint cavity for more than one week and exert long‐lasting lubrication and anti‐inflammatory effects to treat osteoarthritis effectively. This solid–liquid composite lubricating nano‐snowboard provides a new idea for synergistic anti‐inflammatory and lubricating treatment of osteoarthritis.

Improvement of Oral Absorption of Poorly Water-Soluble Drugs by Solid Dispersions with Amphiphilic Phospholipid Polymer

Solid dispersions are one of methods for solubilizing water-insoluble drugs. To enhance the bioavailability, maintenance of the supersaturated state and absorption of the dissolved drug in the gastrointestinal tract are important. We designed and synthesized amphiphilic 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymers as carriers for solid dispersions and evaluated the dissolution behavior in test solutions with different pH and additives. Solid dispersion of troglitazone with amphiphilic MPC copolymers having both aromatic rings and urethane bonds in the side chains showed rapid dissolution and excellent supersaturation maintenance. It was indicated that the balance between the interactions with drug molecules and the water affinity of the polymer should be considered when carriers for solid dispersions are designed. In addition, cell membrane permeability of the solid dispersion with the amphiphilic MPC copolymer was evaluated by the Dissolution / Permeation system, which consists of two liquid chambers and a monolayer of epithelial cells that mimics the intestinal dissolution and permeation process. Further, blood concentration of the drug when solid dispersions were orally administered in mice was also evaluated. The cell membrane permeability and oral absorbability were significantly improved, compared to the solid dispersions with poly(N-vinylpyrrolidone) and suspension or solution of crystalline troglitazone.

Induction of immunogenic cell death in murine colon cancer cells by ferrocene-containing redox phospholipid polymers.

Immunogenic cell death (ICD), activated by damage‐associated molecular patterns (DAMPs), is an apoptotic cell death process that elicits antitumor immunity. Although anticancer drugs that can induce ICD are promising for cancer treatment, the design strategy for ICD inducers remains unclear. In this study, we demonstrated the cell‐penetrating redox phospholipid polymer poly(2‐methacryloyloxyethyl phosphorylcholine‐co‐vinyl ferrocene) (pMFc) inducing ICD in murine colon cancer CT26 cells. pMFc produced oxidative stress by extracting electrons from CT26 cells and induced the release of DAMPs, such as calreticulin, adenosine triphosphate, and high‐mobility group box 1. Moreover, the injection of pMFc‐treated CT26 cells inhibited tumor formation in subsequently challenged CT26 cells, indicating that pMFc elicited antitumor immunity through ICD. Using in vivo therapy, intratumoral injections of pMFc induced complete tumor regression in 20% (1/5) of mice. These results suggested that the redox phospholipid polymer provides a new option for ICD‐inducing anticancer polymers.

Aggregation-Induced Emission Fluorophore-Incorporated Curcumin-Based Ratiometric Nanoprobe for Hypochlorite Detection in Food Matrices.

The development of efficient, economic, reliable, and accurate monitoring of hypochlorite (ClO-) in food matrices is in great demand for food safety assessment, particularly during its massive use against the COVID-19 epidemic. Here, we prepared an aggregation-induced emission (AIE) fluorophore tetraphenylethylene (TPE)-incorporated curcumin-based hybrid ratiometric fluorescence nanoprobe (Curcumin/TPE@HyNPs) through amphiphilic phospholipid polymer-powered nanoprecipitation, which exhibited a fast, highly sensitive, and selective response to the residual ClO- in real food matrices. Because of the inner filter effect (IFE) from curcumin toward TPE inside the nanoprobe, the bright fluorescence of TPE aggregation at ∼437 nm was effectively quenched, along with an enhanced fluorescence of curcumin at ∼478 nm. Once there was a ClO- residue in food matrices, ClO- triggered the oxidation of o-methoxyphenol inside curcumin and led to the almost complete absorption collapse, thereby terminating curcumin fluorescence at ∼478 nm and the IFE process. Accordingly, the fluorescence of TPE at ∼437 nm was recovered. In this case, a ratiometric fluorescent response of Curcumin/TPE@HyNPs toward the residual ClO- in food matrices (e.g., milk) was proposed with a low detection limit of 0.353 μM and a rapid response time of 140.0 s. Notably, the phospholipid polymer as the protection layer effectively reduced/evaded the nonspecific binding of signal reporters inside the nanoprobe, facilitating it to directly monitor the residual ClO- in real food matrices. This work provided a novel approach to utilize the unconventional AIE luminophors for constructing the efficient and reliable early warning mechanisms toward various food contaminants.

Engineering of Portable Smartphone Integrated with Liposome-Encapsulated Curcumin for Onsite Visual Ratiometric Fluorescence Imaging of Hypochlorite.

Precisely onsite monitoring of hypochlorite (ClO- ) is of great significance to guide its rational use, reducing/avoiding its potential threat toward food safety and human health. Considering ClO- could quench fluorescence of curcumin (CCM) by oxidizing the o-methoxyphenol of CCM into benzoquinone, a portable ratiometric fluorescence sensor integrated with smartphone was designed for realizing the visual point-of-care testing (POCT) of ClO- . The amphiphilic phospholipid polymer was used as carrier to wrap curcumin, forming a novel liposome-encapsulated CCM, which provided a scaffold to bind with [Ru(bpy)3 ]2+ through electrostatic interaction, thus assembling [Ru(bpy)3 ]2+ -functionalized liposome-encapsulated CCM ([Ru(bpy)3 ]2+ @CCM-NPs). Further integrated with smartphone, visual imaging of [Ru(bpy)3 ]2+ @CCM-NPs could be achieved and the accurate onsite detection of ClO- could be realized with a detection limit of 66.31 nM and a linear range of 0.2210 to 80.0 μM. In addition, the sensor could monitor ClO- in real samples with an onsite detection time of ∼154.0 s.

Effect of liposome surface modification with water-soluble phospholipid polymer chain-conjugated lipids on interaction with human plasma proteins.

Alternative liposome surface coatings for PEGylation to evade the immune system, particularly the complement system, have garnered significant interest. We previously reported poly(2-methacryloyloxyethyl phosphorylcholine) (MPC)-based lipids (PMPC-lipids) and investigated the surface modification of liposomes. In this study, we synthesize PMPC-lipids with polymerization degrees of 10 (MPC10-lipid), 20 (MPC20-lipid), 50 (MPC50-lipid), and 100 (MPC100-lipid), and coated liposomes with 1, 5, or 10 mol% PMPC-lipids (PMPC-liposomes). Non-modified and PEGylated liposomes are used as controls. We investigate the liposome size, surface charge, polydispersity index, and adsorption of plasma proteins to the liposomes post incubation in human plasma containing N,N,N',N'-ethylenediamine tetraacetic acid (EDTA) or lepirudin by some methods such as sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), western blotting, and automated capillary western blot, with emphasis on the binding of complement protein C3. It is shown that the coating of liposome PMPC-lipids can suppress protein adsorption more effectively with an increase in the molecular weight and molar ratio (1-10 mol%). Apolipoprotein A-I is detected on PMPC-liposomes with a higher molecular weight and higher molar ratio of PMPC-lipids, whereas α2-macroglobulin is detected on non-modified, PEGylated, and PMPC-liposomes with a shorter polymer chain. In addition, a correlation is shown among the PMPC molecular weight, molar ratio, and C3 binding. The MPC10-lipid cannot inhibit C3 binding efficiently, whereas surface modifications with 10 mol% MPC20-lipid and 5 mol% and 10 mol% MPC50-lipid suppress both total protein and C3 binding. Hence, liposome modification with PMPC-lipids can be a possible strategy for avoiding complement activation.

Phospholipid polymer hydrogels with rapid dissociation for reversible cell immobilization.

A reversible and cytocompatible cell immobilization polymer matrix with a rapid dissociation rate was prepared using a zwitterionic phospholipid polymer bearing phenylboronic acid and poly(vinyl alcohol) (PVA). A reversible and spontaneously forming phospholipid polymer hydrogel is reported for use as a cell immobilization matrix which caused no invasive damage to the cells. To improve the possibility of applying the hydrogels as a reversible cell immobilization matrix, the stimuli-responsive dissociation rate of polymer hydrogels was designed to have a more rapid rate to ease the recovery of the immobilized cells. In this study, a phospholipid polymer containing 3-methacrylamide phenylboronic acid (MAPBA) as the phenylboronic acid unit was synthesized. The water-soluble phospholipid polymer (PMB-MAPBA) can spontaneously form polymer hydrogels after mixing with PVA solution under normal pressure, room temperature, and neutral pH conditions. Also, the dissociation of the hydrogels after the addition of D-sorbitol completely occurred within 10 minutes. The cells were easily immobilized on the hydrogels during the preparation process. Also, the recovery ratio of the immobilized cells was improved due to the rapid dissociation of the hydrogels. The reversible and spontaneously formed phospholipid polymer hydrogels are promising for use as soft materials for platforms for cell engineering.

Nanoscaled Morphology and Mechanical Properties of a Biomimetic Polymer Surface on a Silicone Hydrogel Contact Lens.

Materials taking advantage of the characteristics of biological tissues are strongly sought after in medical science and bioscience. On the natural corneal tissue surface, the highly soft and lubricated surface is maintained by composite structures composed of hydrophilic biomolecules and substrates. To mimic this structure, the surface of a silicone hydrogel contact lens was modified with a biomimetic phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), and the nanoscaled morphology and mechanical properties of the surface were confirmed with advanced surface characterization and imaging techniques under an aqueous medium. Concavities and convexities on the nanometer order were recognized on the surface. The surface was completely covered with a PMPC layer and remained intact even after 30 days of clinical use in a human ocular environment. The mechanical properties of the natural corneal tissue and the PMPC-modified surface were similar in the living environment, that is, low modulus and frictional properties comparable to natural tissues. These results show the validity of material preparation by biomimetic methods. The methodologies developed in this study may contribute to future development of human-friendly medical devices.

Liposome-encapsulated aggregation-induced emission fluorogen assisted with portable smartphone for dynamically on-site imaging of residual tetracycline

Reliable on-site monitoring of antibiotic residue is critical to establish the efficient pollution early-warning mechanism for ensuring food safety and environmental health. Herein, we reported the engineering of liposome-encapsulated aggregation-induced emission fluorogen into the portable smartphone for achieving the visual on-site detection of residual tetracycline (TC). Through nanoprecipitation, the aggregation-induced emission fluorogen (AIEgen) tetraphenylethene (TPE) was encapsulated into an amphiphilic phospholipid polymer, affording a scaffold to assemble Eu3+ for forming Eu3+-functionalized liposome-based AIEgen (Eu3+@AIEgen) with bright blue fluorescence at ~456 nm. Upon assistance of citrate, TC was capable of triggering the remarkable fluorescence color change from bright blue (~456 nm) to pink owing to the new red fluorescence emission appeared at ~611 nm, thereby emerging a significant dual-emission for ratiometric response. As expected, an ingenious citrate-assisted Eu3+@AIEgen liposome-based smartphone was proposed to precisely on-site report the residual levels of TC in real sample among the linear range of 0.0961–10.0 μM. Furthermore, this portable sensor exhibited a high sensitivity attributable to the low detection limit of 28.83 nM together with a fast response kinetics of 2.0 min for TC, agreeing well with the demands of on-site assay. This study showed the promising potential for utilizing AIEgen liposome to develop a new category of portable sensors for the point-of-care detection of antibiotic residue in complicated food and environment-related matrixes, which might open a novel way to establish efficient pollution early-warning mechanism for safeguarding public health.

The Process of Binding and Releasing of Genetic Material from Lipoplexes Based on Trimeric Surfactants and Phospholipids.

Nonviral vectors for gene therapy such as lipoplexes are characterized by low toxicity, high biocompatibility, and good transfection efficiency. Specifically, lipoplexes based on polymeric surfactants and phospholipids have great potential as gene carriers due to the increased ability to bind genetic material (multiplied positive electric charge) while lowering undesirable effects (the presence of lipids makes the system more like natural membranes). This study aimed to test the ability to bind and release genetic material by lipoplexes based on trimeric surfactants and lipid formulations of different compositions and to characterize formed complexes by circular dichroism (CD) spectroscopy and atomic force microscopy (AFM). The cytotoxicity of studied lipoplexes was tested on HeLa cells by the MTT cell viability assay and the dye exclusion test (trypan blue). The presence of lipids in the system lowered the surfactant concentration required for complexation (higher efficiency) and reduced the cytotoxicity of lipoplexes. Surfactant/lipids/DNA complexes were more stable than surfactant/DNA complexes. Surfactant molecules induced the genetic material condensation, but the presence of lipids significantly intensified this process. Systems based on trimeric surfactants and lipid formulations, particularly TRI_N and TRI_IMI systems, could be used as delivery carrier, and have proven to be highly effective, nontoxic, and universal for DNA of various lengths.

Anticancer Activity of Cell-Penetrating Redox Phospholipid Polymers.

Redox-active molecules are promising anticancer compounds because cancer cells are vulnerable to oxidative stress. Anticancer drugs are often incorporated into synthetic polymers to improve water solubility, stability, and retention in the body. Most conventional redox-active polymers are regarded as stimuli-responsive polymers, which induce the release of anticancer drugs in response to the surrounding redox environment. Here, we prepared redox phospholipid polymers composed of 2-methacryloyloxyethyl phosphorylcholine units and ferrocene or quinone units as anticancer redox polymers. Redox phospholipid polymers can disturb the intracellular redox state owing to their redox activity and cell membrane permeability. We observed that the redox potential of the polymers affected the reactivity with intracellular redox species and O2, resulting in a different impact on the viability of human cancer and normal cells. Notably, the polymer with moderate reactivity with the intracellular redox species and O2 was shown to suppress the viability of the cancer cells selectively.

Efficacy of hydrated phospholipid polymer interfaces between all-polymer bearings for total hip arthroplasty.

Measurements of wear resistance and metal ion release are important for designing bearing couples or interfaces in total hip arthroplasty (THA). In this study, we investigated wear resistance and metal ion release of surface-modified metal-free all-polymer hip bearings, such as poly(ether-ether-ketone), (PEEK) on cross-linked polyethylene (PEEK-on-CLPE), with a hydrated gel-like surface layer, to propose an improved alternative to the conventional materials used to design THA bearings. The PEEK surface resulted in less metal ion release than the cobalt-chromium-molybdenum (Co-Cr-Mo) alloy surface owing to the lack of metal. The PEEK-on-CLPE bearing (6.33 mg/106 cycles) had lower wear (rate) than the bearing with Co-Cr-Mo alloy-on-CLPE (10.47 mg/106 cycles) under controlled laboratory conditions; the wear performance of the all-polymer hip bearings was further improved with hemi- or both-surface modified with a hydrated poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) layer (3.74 and 3.06 mg/106 cycles, respectively). The PMPC-grafted interface of PEEK-on-CLPE will be especially suitable for THA candidates. This study is of key importance for the design of lifelong THA and a better understanding of the limitations resulting from using PEEK. Further studies are necessary to evaluate the possibility of using this material in artificial hips.

Design of Intelligent Interface Based on Cytocompatible Polymers for Control on Cell Function

Bioinspired polymeric biomaterials with excellent cytocompatibility have been designed in this study. 2-Methacryloyloxyehtyl phosphorylcholine (MPC) is a phospholipid polymer and an essential polymeric biomaterial, which has been used in various biomedical and pharmaceutical applications including implantable medical devices. Furthermore, it is a methacrylate monomer unit and can be copolymerized with other vinyl monomers via conventional radical polymerization. The water-solubility of MPC polymers depends on the molecular composition and molecular weight of the polymers. PMB is a water-soluble polymer copolymerized with hydrophobic n-butyl methacrylate, and can be used as a solubilizing agent for poorly soluble drugs. The phospholipid polymers showed low cytotoxicity, and the solubilized drugs effectively not only penetrated into the cells but also into the surrounding tissues. In addition, the water-soluble MPC polymer containing a phenylboronic acid moiety was observed to spontaneously form polymeric hydrogels with polyol compounds. The reversible polymer hydrogels were used as artificial extracellular matrices for cell immobilization and cell engineering. Polymeric biomaterials with intelligent interfaces might be explored as innovative techniques for application in pharmaceutical and life sciences.