The Experts below are selected from a list of 732 Experts worldwide ranked by ideXlab platform
Xianzhu Yang - One of the best experts on this subject based on the ideXlab platform.
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Tumor Acidity/NIR Controlled Interaction of Transformable Nanoparticle with Biological Systems for Cancer Therapy
2017Co-Authors: Wei Tao, Xianzhu Yang, Jun WangAbstract:Precisely controlling the interaction of nanoparticles with biological systems (nanobio interactions) from the injection site to biological targets shows great potential for biomedical applications. Inspired by the ability of nanoparticles to alter their physicochemical properties according to different stimuli, we explored the tumor acidity and near-infrared (NIR) light activated transformable nanoparticle DATAT-NPIR&DOX. This nanoparticle consists of a tumor acidity-activated TAT [the TAT lysine residues’ amines was modified with 2,3-dimethylmaleic anhydride (DA)], a flexible chain Polyphosphoester core coencapsulated a NIR dye IR-780, and DOX (doxorubicin). The physicochemical properties of the nanoparticle can be controlled in a stepwise fashion using tumor acidity and NIR light, resulting in adjustable nanobio interactions. The resulting transformable nanoparticle DATAT-NPIR&DOX efficiently avoids the interaction with mononuclear phagocyte system (MPS) (“stealth” state) due to the masking of the TAT peptide during blood circulation. Once it has accumulated in the tumor tissues, DATAT-NPIR&DOX is reactivated by tumor acidity and transformed into the “recognize” state in order to promote interaction with tumor cells and enhance cellular internalization. Then, this nanoparticle is transformed into “attack” state under NIR irradiation, achieving the supersensitive DOX release from the flexible chain Polyphosphoester core in order to increase the DOX–DNA interaction. This concept provides new avenues for the creation of transformable drug delivery systems that have the ability to control nanobio interactions
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Redox-Responsive Polyphosphoester-Based Micellar Nanomedicines for Overriding Chemoresistance in Breast Cancer Cells.
ACS applied materials & interfaces, 2015Co-Authors: Junxia Wang, Chun-yang Sun, Yucai Wang, Wei Tao, Haisheng Qian, Feng Fan, Xianzhu YangAbstract:Multidrug resistance (MDR) has been recognized as a key factor contributing to the failure of chemotherapy for cancer in the clinic, often due to insufficient delivery of anticancer drugs to target cells. For addressing this issue, a redox-responsive Polyphosphoester-based micellar nanomedicine, which can be triggered to release transported drugs in tumor cells, has been developed. The micelles are composed of diblock copolymers with a hydrophilic PEG block and a hydrophobic Polyphosphoester (PPE) block bearing a disulfide bond in a side group. After incubating the redox-responsive micelles with drug-resistant tumor cells, the intracellular accumulation and retention of DOX were significantly enhanced. Moreover, after internalization by MDR cancer cells, the disulfide bond in the side group was cleaved by the high intracellular glutathione levels, resulting in a hydrophobic to hydrophilic transition of the PPE block and subsequent disassembly of the micelles. Thus, the encapsulated DOX was rapidly release...
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A block copolymer of zwitterionic Polyphosphoester and polylactic acid for drug delivery.
Biomaterials science, 2015Co-Authors: Rong Sun, Chun-yang Sun, Xianzhu Yang, Song Shen, Yang Liu, Yan Bao, Yan-hua Zhu, Jun WangAbstract:Polymeric nanoparticles have been widely used as nano-drug delivery systems in preclinical and clinical trials for cancer therapy, and these systems usually need to be sterically stabilized by poly(ethylene glycol) (PEG) to maintain stability and avoid rapid clearance by the immune system. Recently, zwitterionic materials have been demonstrated to be potential alternatives to the classic PEG. Herein, we developed two drug delivery systems stabilized by zwitterionic Polyphosphoesters. These nanoparticles showed favourable stability and anti-protein absorption ability in vitro. Meanwhile, as drug carriers, these zwitterionic Polyphosphoester-stabilized nanoparticles significantly prolonged drug circulation half-lives and increased drug accumulation in tumors, which was comparable to PEG-stabilized nanoparticles. Systemic delivery of doxorubicin (DOX) by zwitterionic Polyphosphoester-stabilized nanoparticles significantly inhibited tumor growth in a MDA-MB-231 tumor model, suggesting the potential of zwitterionic Polyphosphoester-based nanoparticles in anticancer drug delivery.
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Chlorin e6-Encapsulated Polyphosphoester Based Nanocarriers with Viscous Flow Core for Effective Treatment of Pancreatic Cancer
2015Co-Authors: Fei Ding, Junxia Wang, Yan-hua Zhu, Wei Tao, Xianzhu YangAbstract:Lack of effective treatment results in the low survival for patients with pancreatic cancer, and photodynamic therapy (PDT) with photosensitizers has emerged as an effective therapeutic option for treatment of various tumors by light-generated cytotoxic reactive oxygen species (ROS) to induce cell apoptosis or necrosis. However, the poor solubility, rapid blood clearance, and weak internalization of the photosensitizer seriously inhibit its anticancer efficacy. To overcome these obstacles, a Polyphosphoester-based nanocarrier (NP-PPE) is employed as the carrier of the hydrophobic photosensitizer, chlorin e6 (Ce6), for photodynamic therapy. The Ce6-encapsulated nanocarrier (NP-PPE/Ce6) significantly promoted the cellular internalization of Ce6, enhanced the generation of ROS in the tumor cells after irradiation. Therefore, the cellular phototoxicity of NP-PPE/Ce6 against BxPC-3 pancreatic cancer cells was markedly enhanced than that of free Ce6 in vitro. Furthermore, NP-PPE/Ce6 improved accumulation of Ce6 in tumor tissue and treatment with NP-PPE/Ce6 significantly enhanced antitumor efficacy in human BxPC-3 pancreatic cancer xenografts. These results suggest that using a Polyphosphoester-based nanocarrier as the delivery system for a photosensitizer has great potential for PDT of pancreatic cancer
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Redox-Responsive Polyphosphoester-Based Micellar Nanomedicines for Overriding Chemoresistance in Breast Cancer Cells
2015Co-Authors: Junxia Wang, Chun-yang Sun, Yucai Wang, Wei Tao, Haisheng Qian, Feng Fan, Xianzhu YangAbstract:Multidrug resistance (MDR) has been recognized as a key factor contributing to the failure of chemotherapy for cancer in the clinic, often due to insufficient delivery of anticancer drugs to target cells. For addressing this issue, a redox-responsive Polyphosphoester-based micellar nanomedicine, which can be triggered to release transported drugs in tumor cells, has been developed. The micelles are composed of diblock copolymers with a hydrophilic PEG block and a hydrophobic Polyphosphoester (PPE) block bearing a disulfide bond in a side group. After incubating the redox-responsive micelles with drug-resistant tumor cells, the intracellular accumulation and retention of DOX were significantly enhanced. Moreover, after internalization by MDR cancer cells, the disulfide bond in the side group was cleaved by the high intracellular glutathione levels, resulting in a hydrophobic to hydrophilic transition of the PPE block and subsequent disassembly of the micelles. Thus, the encapsulated DOX was rapidly released, and abrogation of drug resistance in the cancer cells was observed in vitro. Moreover, the DOX-loaded redox-responsive micelles exhibited significantly enhanced inhibition of tumor growth in nude mice bearing MCF-7/ADR xenograft tumors via tail vein injection, indicating that such micelles have great potential in overcoming MDR for cancer therapy
Jun Wang - One of the best experts on this subject based on the ideXlab platform.
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Tumor Acidity/NIR Controlled Interaction of Transformable Nanoparticle with Biological Systems for Cancer Therapy
2017Co-Authors: Wei Tao, Xianzhu Yang, Jun WangAbstract:Precisely controlling the interaction of nanoparticles with biological systems (nanobio interactions) from the injection site to biological targets shows great potential for biomedical applications. Inspired by the ability of nanoparticles to alter their physicochemical properties according to different stimuli, we explored the tumor acidity and near-infrared (NIR) light activated transformable nanoparticle DATAT-NPIR&DOX. This nanoparticle consists of a tumor acidity-activated TAT [the TAT lysine residues’ amines was modified with 2,3-dimethylmaleic anhydride (DA)], a flexible chain Polyphosphoester core coencapsulated a NIR dye IR-780, and DOX (doxorubicin). The physicochemical properties of the nanoparticle can be controlled in a stepwise fashion using tumor acidity and NIR light, resulting in adjustable nanobio interactions. The resulting transformable nanoparticle DATAT-NPIR&DOX efficiently avoids the interaction with mononuclear phagocyte system (MPS) (“stealth” state) due to the masking of the TAT peptide during blood circulation. Once it has accumulated in the tumor tissues, DATAT-NPIR&DOX is reactivated by tumor acidity and transformed into the “recognize” state in order to promote interaction with tumor cells and enhance cellular internalization. Then, this nanoparticle is transformed into “attack” state under NIR irradiation, achieving the supersensitive DOX release from the flexible chain Polyphosphoester core in order to increase the DOX–DNA interaction. This concept provides new avenues for the creation of transformable drug delivery systems that have the ability to control nanobio interactions
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A block copolymer of zwitterionic Polyphosphoester and polylactic acid for drug delivery.
Biomaterials science, 2015Co-Authors: Rong Sun, Chun-yang Sun, Xianzhu Yang, Song Shen, Yang Liu, Yan Bao, Yan-hua Zhu, Jun WangAbstract:Polymeric nanoparticles have been widely used as nano-drug delivery systems in preclinical and clinical trials for cancer therapy, and these systems usually need to be sterically stabilized by poly(ethylene glycol) (PEG) to maintain stability and avoid rapid clearance by the immune system. Recently, zwitterionic materials have been demonstrated to be potential alternatives to the classic PEG. Herein, we developed two drug delivery systems stabilized by zwitterionic Polyphosphoesters. These nanoparticles showed favourable stability and anti-protein absorption ability in vitro. Meanwhile, as drug carriers, these zwitterionic Polyphosphoester-stabilized nanoparticles significantly prolonged drug circulation half-lives and increased drug accumulation in tumors, which was comparable to PEG-stabilized nanoparticles. Systemic delivery of doxorubicin (DOX) by zwitterionic Polyphosphoester-stabilized nanoparticles significantly inhibited tumor growth in a MDA-MB-231 tumor model, suggesting the potential of zwitterionic Polyphosphoester-based nanoparticles in anticancer drug delivery.
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Surface-modulated and thermoresponsive Polyphosphoester nanoparticles for enhanced intracellular drug delivery
Science China Chemistry, 2014Co-Authors: Feng Wang, Xianzhu Yang, Tianmeng Sun, Jun WangAbstract:The chemical structure of end groups influenced the phase transition temperature of thermoresponsive polymers. We demonstrated a strategy for the preparation of the pH/thermo-responsive polymeric nanoparticles via subtle modification of end groups of thermoresponsive polymer segments with a carboxyl group and revealed its potential application for enhanced intracellular drug delivery. By developing a polymeric nanoparticle composed of poly(aliphatic ester) as the inner core and thermoresponsive Polyphosphoester as the outer shell, we showed that end groups of thermoresponsive Polyphosphoester segments modified by carboxyl groups exhibited a pH/thermo-responsive behavior due to the hydrophilic to hydrophobic transitions of the end groups in response to the pH. Moreover, by encapsulating doxorubicin into the hydrophobic core of such pH/thermo-responsive polymer nanoparticles, their intracellular delivery and cytotoxicity to wild-type and drug-resistant tumor cells were significantly enhanced through the phase-transition-dependent drug release that was triggered by endosomal/lysosomal pH. This novel strategy and the multi-responsive polymer nanoparticles achieved by the subtle chain-terminal modification of thermoresponsive polymers provide a smart platform for biomedical applications.
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Doxorubicin Conjugate of Poly(Ethylene Glycol)-Block-Polyphosphoester for Cancer Therapy
Advanced healthcare materials, 2013Co-Authors: Chun-yang Sun, Shuang Dou, Xianzhu Yang, Jun WangAbstract:Polyphosphoesters with repeating phosphoester linkages in the backbone can be easily functionalized, are biodegradable and potentially biocompatible, and may be potential candidates as polymer carriers of drug conjugates. Here, the efficacy of a Polyphosphoester drug conjugate as an anticancer agent in vivo is assessed for the first time. With controlled synthesis, doxorubicin conjugated to poly(ethylene glycol)-block-Polyphosphoester (PPEH-DOX) via labile hydrazone bonds form spherical nanoparticles in aqueous solution with an average diameter of ≈60 nm. These nanoparticles are effectively internalized by MDA-MB-231 breast cancer cells and release the conjugated doxorubicin in response to the intracellular pH of endosomes and lysosomes, resulting in significant antiproliferative activity in cancer cells. Compared with free doxorubicin injection, PPEH-DOX injection exhibits much longer circulation behavior in the plasma of mice and leads to enhanced drug accumulation in tumor cells. In an MDA-MB-231 xenograft murine model, inhibition of tumor growth with systemic delivery of PPEH-DOX nanoparticles is more pronounced compared with free doxorubicin injection, suggesting the potential of Polyphosphoesters as carriers of drug conjugates in cancer therapy.
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lipase sensitive polymeric triple layered nanogel for on demand drug delivery
Journal of the American Chemical Society, 2012Co-Authors: Menghua Xiong, Xianzhu Yang, Yan Bao, Yucai Wang, Baolin Sun, Jun WangAbstract:We report a new strategy for differential delivery of antimicrobials to bacterial infection sites with a lipase-sensitive polymeric triple-layered nanogel (TLN) as the drug carrier. The TLN was synthesized by a convenient arm-first procedure using an amphiphilic diblock copolymer, namely, monomethoxy poly(ethylene glycol)-b-poly(e-caprolactone), to initiate the ring-opening polymerization of the difunctional monomer 3-oxapentane-1,5-diyl bis(ethylene phosphate). The hydrophobic poly(e-caprolactone) (PCL) segments collapsed and surrounded the Polyphosphoester core, forming a hydrophobic and compact molecular fence in aqueous solution which prevented antibiotic release from the Polyphosphoester core prior to reaching bacterial infection sites. However, once the TLN sensed the lipase-secreting bacteria, the PCL fence of the TLN degraded to release the antibiotic. Using Staphylococcus aureus (S. aureus) as the model bacterium and vancomycin as the model antimicrobial, we demonstrated that the TLN released alm...
Karen L. Wooley - One of the best experts on this subject based on the ideXlab platform.
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Development of Fully Degradable Phosphonium-Functionalized Amphiphilic Diblock Copolymers for Nucleic Acids Delivery
2018Co-Authors: Yannick P. Borguet, Mahmoud Elsabahy, Sarosh Khan, Amandine Noel, Sean P. Gunsten, Steven L. Brody, Karen L. WooleyAbstract:To expand the range of functional polymer materials to include fully hydrolytically degradable systems that bear bioinspired phosphorus-containing linkages both along the backbone and as cationic side chain moieties for packaging and delivery of nucleic acids, phosphonium-functionalized Polyphosphoester-block-poly(l-lactide) copolymers of various compositions were synthesized, fully characterized, and their self-assembly into nanoparticles were studied. First, an alkyne-functionalized Polyphosphoester-block-poly(l-lactide) copolymer was synthesized via a one pot sequential ring opening polymerization of an alkyne-functionalized phospholane monomer, followed by the addition of l-lactide to grow the second block. Second, the alkynyl side groups of the Polyphosphoester block were functionalized via photoinitiated thiol–yne radical addition of a phosphonium-functionalized free thiol. The polymers of varying phosphonium substitution degrees were self-assembled in aqueous buffers to afford formation of well-defined core–shell assemblies with an average size ranging between 30 and 50 nm, as determined by dynamic light scattering. Intracellular delivery of the nanoparticles and their effects on cell viability and capability at enhancing transfection efficiency of nucleic acids (e.g., siRNA) were investigated. Cell viability assays demonstrated limited toxicity of the assembly to RAW 264.7 mouse macrophages, except at high polymer concentrations, where the polymer of high degree of phosphonium functionalization induced relatively higher cytotoxicity. Transfection efficiency was strongly affected by the phosphonium-to-phosphate (P+/P–) ratios of the polymers and siRNA, respectively. The AllStars Hs Cell Death siRNA complexed to the various copolymers at a P+/P– ratio of 10:1 induced comparable cell death to Lipofectamine. These fully degradable nanoparticles might provide biocompatible nanocarriers for therapeutic nucleic acid delivery
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Rapid and Versatile Construction of Diverse and Functional Nanostructures Derived from a Polyphosphoester-Based Biomimetic Block Copolymer System
2016Co-Authors: Shiyi Zhang, Jiong Zou, Fuwu Zhang, Mahmoud Elsabahy, Simcha E. Felder, Jiahua Zhu, Darrin J. Pochan, Karen L. WooleyAbstract:A rapid and efficient approach for the preparation and modification of a versatile class of functional polymer nanoparticles has been developed, for which the entire engineering process from small molecules to polymers to nanoparticles bypasses typical slow and inefficient procedures and rather employs a series of steps that capture fully the “click” chemistry concepts that have greatly facilitated the preparation of complex polymer materials over the past decade. The construction of various nanoparticles with functional complexity from a versatile platform is a challenging aim to provide materials for fundamental studies and also optimization toward a diverse range of applications. In this paper, we demonstrate the rapid and facile preparation of a family of nanoparticles with different surface charges and functionalities based on a biodegradable Polyphosphoester block copolymer system. From a retrosynthetic point of view, the nonionic, anionic, cationic, and zwitterionic micelles with hydrodynamic diameters between 13 and 21 nm and great size uniformity were quickly formed by suspending, independently, four amphiphilic diblock Polyphosphoesters into water, which were functionalized from the same parental hydrophobic-functional AB diblock Polyphosphoester by click-type thiol–yne reactions. The well-defined (PDI < 1.2) hydrophobic-functional AB diblock Polyphosphoester was synthesized by an ultrafast (
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Degradable Polyphosphoester-based silver-loaded nanoparticles as therapeutics for bacterial lung infections
Nanoscale, 2015Co-Authors: Fuwu Zhang, Shiyi Zhang, Hai Wang, Sangho Cho, Justin A. Smolen, Parth N. Shah, Jeffery E. Raymond, Carolyn L. Cannon, Karen L. WooleyAbstract:In this study, a new type of degradable Polyphosphoester-based polymeric nanoparticle, capable of carrying silver cations via interactions with alkyne groups, has been developed as a potentially effective and safe treatment for lung infections. It was found that up to 15% (w/w) silver loading into the nanoparticles could be achieved, consuming most of the pendant alkyne groups along the backbone, as revealed by Raman spectroscopy. The well-defined Ag-loaded nanoparticles released silver in a controlled and sustained manner over 5 days, and displayed enhanced in vitro antibacterial activities against cystic fibrosis-associated pathogens and decreased cytotoxicity to human bronchial epithelial cells, in comparison to silver acetate.
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poly ethylene oxide block Polyphosphoester graft paclitaxel conjugates with acid labile linkages as a ph sensitive and functional nanoscopic platform for paclitaxel delivery
Advanced Healthcare Materials, 2014Co-Authors: Jiong Zou, Shiyi Zhang, Fuwu Zhang, Mahmoud Elsabahy, Jingwei Fan, Stephanie F Pollack, Karen L. WooleyAbstract:There has been an increasing interest to develop new types of stimuli-responsive drug delivery vehicles with high drug loading and controlled release properties for chemotherapeutics. An acid-labile, Polyphosphoester-based degradable, polymeric paclitaxel (PTX) conjugate containing ultra-high levels of PTX loading has been improved significantly, in this second generation development, which involves connection of each PTX molecule to the polymer backbone via a pH-sensitive β-thiopropionate linkage. The results for this system indicate that it has great potential as an effective anti-cancer agent. Poly(ethylene oxide)-block-Polyphosphoester-graft-PTX drug conjugate (PEO-b-PPE-g-PTX G2) was synthesized by organocatalyst-promoted ring-opening polymerization of 2-(but-3-en-1-yloxy)-1,3,2-dioxaphospholane-2-oxide from a PEO macroinitiator, followed by thermo-promoted thiolene click conjugation of a thiol-functionalized PTX prodrug to the pendant alkene groups of the block copolymer. The PEO-b-PPE-g-PTX G2 formed well-defined nanoparticles in aqueous solution, by direct dissolution into water, with a number-averaged hydrodynamic diameter of 114 ± 31 nm. The conjugate had PTX loading capacity as high as 53 wt%, and a maximum PTX concentration of 0.68 mg/mL in water (vs. 1.7 μg/mL for free PTX). Although the PTX concentration is ca. 10× less than for our first generation material, its accelerated release allowed for similar free PTX concentrations vs. time. The PEO-b-PPE-g-PTX G2 exhibited accelerated drug release under acidic conditions (~50 wt% PTX released in 8 d) compared to neutral conditions (~20 wt% PTX released in 8 d) and compared to the first generation analog that contained ester linkages between PTX and the polymer backbone (<5 wt% PTX released in 4 d), due to their acid-sensitive hydrolytically-labile β-thiopropionate linkages between PTX molecules and the polymer backbone. The positive cell-killing activity of PEO-b-PPE-g-PTX G2 against two cancer cell lines was demonstrated, and the presence of pendant reactive functionality provides a powerful platform for future work to involve conjugation of multiple numbers and/or types of targeting ligands, other drugs and imaging agents to achieve chemotherapy and bioimaging. Compared to our previously reported Polyphosphoester-based PTX drug conjugates, PEO-b-PPE-g-PTX G1 without the β-thiopropionate linker, the PEO-b-PPE-g-PTX G2 showed pH-triggered drug release property and 5-to-8-fold enhanced in vitro cytotoxcity against two cancer cell lines.
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Surface Charges and Shell Crosslinks Each Play Significant Roles in Mediating Degradation, Biofouling, Cytotoxicity and Immunotoxicity for Polyphosphoester-based Nanoparticles
Scientific reports, 2013Co-Authors: Mahmoud Elsabahy, Shiyi Zhang, Fuwu Zhang, Zhou J. Deng, Young H. Lim, Hai Wang, Perouza Parsamian, Paula T. Hammond, Karen L. WooleyAbstract:Surface Charges and Shell Crosslinks Each Play Significant Roles in Mediating Degradation, Biofouling, Cytotoxicity and Immunotoxicity for Polyphosphoester-based Nanoparticles
Frederik R. Wurm - One of the best experts on this subject based on the ideXlab platform.
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Polyphosphoester surfactants as general stealth coatings for polymeric nanocarriers
Acta biomaterialia, 2020Co-Authors: Kristin N. Bauer, Johanna Simon, Volker Mailänder, Katharina Landfester, Frederik R. WurmAbstract:Opsonization of nanocarriers is one of the most important biological barriers for controlled drug delivery. The typical way to prevent such unspecific protein adsorption and thus fast clearance by the immune system is the covalent modification of drug delivery vehicles with poly(ethylene glycol) (PEG), so-called PEGylation. Recently, Polyphosphoesters (PPEs) were identified as adequate PEG substitutes, however with the benefits of controllable hydrophilicity, additional chemical functionality, or biodegradability. Here, we present a general strategy by non-covalent adsorption of different nonionic PPE-surfactants to nanocarriers with stealth properties. Polyphosphoester surfactants with different binding motifs were synthesized by anionic ring-opening polymerization of cyclic phosphates or phosphonates and well-defined polymers were obtained. They were evaluated with regard to their cytotoxicity, protein interactions, and corona formation and their cellular uptake. We proved that all PPE-surfactants have lower cytotoxicity as the common PEG-based surfactant (Lutensol® AT 50) and that their hydrolysis is controlled by their chemical structure. Two polymeric nanocarriers, namely polystyrene and poly(methyl methacrylate), and bio-based and potentially biodegradable hydroxyethyl starch nanocarriers were coated with the PPE-surfactants. All nanocarriers exhibited reduced protein adsorption after coating with PPE-surfactants and a strongly reduced interaction with macrophages. This general strategy allows the transformation of polymeric nanocarriers into camouflaged nanocarriers and by the chemical versatility of PPEs will allow the attachment of additional moieties for advanced drug delivery.
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hydrophilic Polyphosphoester conjugated fluorinated chlorin as an entirely biodegradable nano photosensitizer for reliable and efficient photodynamic therapy
Chemical Communications, 2020Co-Authors: Zhiyong Liu, Frederik R. Wurm, Yudong Xue, Chao Chen, Minbo Lan, Weian ZhangAbstract:An entirely biodegradable nano-photosensitizer platform (PPE-FP2) was fabricated by conjugating the photosensitizer TFPC to hydrophilic Polyphosphoesters (PPEs) for efficiently liberating photosensitizers at the tumor site. The complete biodegradability of PPE-FP2 avoided residual nanoparticles in vivo after therapy, realizing reliable and effective photodynamic therapy.
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Nanoscopic hydrophilic/hydrophilic phase-separation well below the LCST of Polyphosphoesters.
Chemical communications (Cambridge England), 2019Co-Authors: Johannes Hunold, Frederik R. Wurm, Thomas Wolf, Dariush HinderbergerAbstract:The complex phase separation process of thermoresponsive Polyphosphoesters (PPEs) with an identical side-group structure but different copolymer compositions is characterized by electron paramagnetic resonance (EPR) spectroscopy. In water these PPEs show LCST-type behavior, in which water-rich and slightly polymer-enriched nanoscopic regions are highly water swollen, and nanoscopic inhomogeneities with the lowest polarity contrast measured so far develop 8 °C below the macroscopic cloud point.
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Interfacial Conformation of Hydrophilic Polyphosphoesters Affects Blood Protein Adsorption
ACS applied materials & interfaces, 2018Co-Authors: Christoph Bernhard, Kristin N. Bauer, Mischa Bonn, Frederik R. Wurm, Grazia GonellaAbstract:Synthetic polymers are commonly used as protein repelling materials for a variety of biomedical applications. Despite their widespread use, the fundamental mechanism underlying protein repellence is often elusive. Such insights are essential for improving existing and developing new materials. Here, we investigate how subtle differences in the chemistry of hydrophilic Polyphosphoesters influence the adsorption of the human blood proteins serum albumin and fibrinogen. Using thermodynamic measurements, surface-specific vibrational spectroscopy, and Brewster angle microscopy, we investigate protein adsorption, hydration, and steric repulsion properties of the Polyphosphoester polymers. Whereas both surface hydration and polymer conformation of the polymers vary substantially as a consequence of the chemical differences in the polymer structure, the protein repellency ability of these hydrophilic materials appears to be dominated by steric repulsion.
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Interfacial Conformation of Hydrophilic Polyphosphoesters Affects Blood Protein Adsorption
2018Co-Authors: Christoph Bernhard, Kristin N. Bauer, Mischa Bonn, Frederik R. Wurm, Grazia GonellaAbstract:Synthetic polymers are commonly used as protein repelling materials for a variety of biomedical applications. Despite their widespread use, the fundamental mechanism underlying protein repellence is often elusive. Such insights are essential for improving existing and developing new materials. Here, we investigate how subtle differences in the chemistry of hydrophilic Polyphosphoesters influence the adsorption of the human blood proteins serum albumin and fibrinogen. Using thermodynamic measurements, surface-specific vibrational spectroscopy, and Brewster angle microscopy, we investigate protein adsorption, hydration, and steric repulsion properties of the Polyphosphoester polymers. Whereas both surface hydration and polymer conformation of the polymers vary substantially as a consequence of the chemical differences in the polymer structure, the protein repellency ability of these hydrophilic materials appears to be dominated by steric repulsion
Shiyi Zhang - One of the best experts on this subject based on the ideXlab platform.
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Design and development of multifunctional Polyphosphoester-based nanoparticles for ultrahigh paclitaxel dual loading
Nanoscale, 2017Co-Authors: Fuwu Zhang, Shiyi Zhang, Mahmoud Elsabahy, Sarosh Khan, Justin A. Smolen, Guizhi Zhu, Ashlee A. Jahnke, Xiaoyuan ChenAbstract:Multifunctional Polyphosphoester-based nanoparticles capable of loading paclitaxel (PTX) both chemically and physically were prepared, achieving an ultrahigh equivalent PTX aqueous concentration of 25.30 mg mL-1. The dual-loaded nanoparticles were effective in killing cancer cells, which has the potential to minimize the amount of nanocarriers needed for clinical applications, due to their ultrahigh loading capacity.
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Rapid and Versatile Construction of Diverse and Functional Nanostructures Derived from a Polyphosphoester-Based Biomimetic Block Copolymer System
2016Co-Authors: Shiyi Zhang, Jiong Zou, Fuwu Zhang, Mahmoud Elsabahy, Simcha E. Felder, Jiahua Zhu, Darrin J. Pochan, Karen L. WooleyAbstract:A rapid and efficient approach for the preparation and modification of a versatile class of functional polymer nanoparticles has been developed, for which the entire engineering process from small molecules to polymers to nanoparticles bypasses typical slow and inefficient procedures and rather employs a series of steps that capture fully the “click” chemistry concepts that have greatly facilitated the preparation of complex polymer materials over the past decade. The construction of various nanoparticles with functional complexity from a versatile platform is a challenging aim to provide materials for fundamental studies and also optimization toward a diverse range of applications. In this paper, we demonstrate the rapid and facile preparation of a family of nanoparticles with different surface charges and functionalities based on a biodegradable Polyphosphoester block copolymer system. From a retrosynthetic point of view, the nonionic, anionic, cationic, and zwitterionic micelles with hydrodynamic diameters between 13 and 21 nm and great size uniformity were quickly formed by suspending, independently, four amphiphilic diblock Polyphosphoesters into water, which were functionalized from the same parental hydrophobic-functional AB diblock Polyphosphoester by click-type thiol–yne reactions. The well-defined (PDI < 1.2) hydrophobic-functional AB diblock Polyphosphoester was synthesized by an ultrafast (
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Degradable Polyphosphoester-based silver-loaded nanoparticles as therapeutics for bacterial lung infections
Nanoscale, 2015Co-Authors: Fuwu Zhang, Shiyi Zhang, Hai Wang, Sangho Cho, Justin A. Smolen, Parth N. Shah, Jeffery E. Raymond, Carolyn L. Cannon, Karen L. WooleyAbstract:In this study, a new type of degradable Polyphosphoester-based polymeric nanoparticle, capable of carrying silver cations via interactions with alkyne groups, has been developed as a potentially effective and safe treatment for lung infections. It was found that up to 15% (w/w) silver loading into the nanoparticles could be achieved, consuming most of the pendant alkyne groups along the backbone, as revealed by Raman spectroscopy. The well-defined Ag-loaded nanoparticles released silver in a controlled and sustained manner over 5 days, and displayed enhanced in vitro antibacterial activities against cystic fibrosis-associated pathogens and decreased cytotoxicity to human bronchial epithelial cells, in comparison to silver acetate.
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Improving Paclitaxel Delivery: In Vitro and In Vivo Characterization of PEGylated Polyphosphoester-Based Nanocarriers
Journal of the American Chemical Society, 2015Co-Authors: Fuwu Zhang, Shiyi Zhang, Jiong Zou, Adriana Pavía-sanders, Jingwei Fan, Stephanie F Pollack, Sarah E. Leininger, Amelia M. Gonzalez, Rachel JohnsonAbstract:Nanomaterials have great potential to offer effective treatment against devastating diseases by providing sustained release of high concentrations of therapeutic agents locally, especially when the route of administration allows for direct access to the diseased tissues. Biodegradable Polyphosphoester-based polymeric micelles and shell cross-linked knedel-like nanoparticles (SCKs) have been designed from amphiphilic block-graft terpolymers, PEBP-b-PBYP-g-PEG, which effectively incorporate high concentrations of paclitaxel (PTX). Well-dispersed nanoparticles physically loaded with PTX were prepared, exhibiting desirable physiochemical characteristics. Encapsulation of 10 wt% PTX, into either micelles or SCKs, allowed for aqueous suspension of PTX at concentrations up to 4.8 mg/mL, as compared to
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Improving Paclitaxel Delivery: In Vitro and In Vivo Characterization of PEGylated Polyphosphoester-Based Nanocarriers
2015Co-Authors: Fuwu Zhang, Shiyi Zhang, Jiong Zou, Jingwei Fan, Stephanie F. Pollack, Amelia M. Gonzalez, Sarah E. Leininger, Adriana Pavía-sanders, Rachel JohnsonAbstract:Nanomaterials have great potential to offer effective treatment against devastating diseases by providing sustained release of high concentrations of therapeutic agents locally, especially when the route of administration allows for direct access to the diseased tissues. Biodegradable Polyphosphoester-based polymeric micelles and shell cross-linked knedel-like nanoparticles (SCKs) have been designed from amphiphilic block-graft terpolymers, PEBP-b-PBYP-g-PEG, which effectively incorporate high concentrations of paclitaxel (PTX). Well-dispersed nanoparticles physically loaded with PTX were prepared, exhibiting desirable physiochemical characteristics. Encapsulation of 10 wt% PTX, into either micelles or SCKs, allowed for aqueous suspension of PTX at concentrations up to 4.8 mg/mL, as compared to