Showing papers by "Guanghui Ma published in 2016"

An Injectable Self-Assembling Collagen-Gold Hybrid Hydrogel for Combinatorial Antitumor Photothermal/Photodynamic Therapy.

Abstract: An injectable and self-healing collagen-gold hybrid hydrogel is spontaneously formed by electrostatic self-assembly and subsequent biomineralization. It is demonstrated that such collagen-based hydrogels may be used as an injectable material for local delivery of therapeutic agents, showing enhanced antitumor efficacy.

Simple Peptide-Tuned Self-Assembly of Photosensitizers towards Anticancer Photodynamic Therapy.

Abstract: Peptide-tuned self-assembly of functional components offers a strategy towards improved properties and unique functions of materials, but the requirement of many different functions and a lack of understanding of complex structures present a high barrier for applications. Herein, we report a photosensitive drug delivery system for photodynamic therapy (PDT) by a simple dipeptide- or amphiphilic amino-acid-tuned self-assembly of photosensitizers (PSs). The assembled nanodrugs exhibit multiple favorable therapeutic features, including tunable size, high loading efficiency, and on-demand drug release responding to pH, surfactant, and enzyme stimuli, as well as preferable cellular uptake and biodistribution. These features result in greatly enhanced PDT efficacy invitro and invivo, leading to almost complete tumor eradication in mice receiving a single drug dose and a single exposure to light.

Recent Studies of Pickering Emulsions: Particles Make the Difference

Abstract: In recent years, emulsions stabilized by micro- or nanoparticles (known as Pickering emulsions) have attracted much attention. Micro- or nanoparticles, as the main components of the emulsion, play a key role in the preparation and application of Pickering emulsions. The existence of particles at the interface between the oil and aqueous phases affects not only the preparation, but also the properties of Pickering emulsions, affording superior stability, low toxicity, and stimuli-responsiveness compared to classical emulsions stabilized by surfactants. These advantages of Pickering emulsions make them attractive, especially in biomedicine. In this review, the effects of the characteristics of micro- and nanoparticles on the preparation and properties of Pickering emulsions are introduced. In particular, the preparation methods of Pickering emulsions, especially uniform-sized emulsions, are listed. Uniform Pickering emulsions are convenient for both mechanistic research and applications. Furthermore, some biomedical applications of Pickering emulsions are discussed and the problems hindering their clinical application are identified.

Multi-shelled metal oxides prepared via an anion-adsorption mechanism for lithium-ion batteries

Abstract: One of the major problems in the development of lithium-ion batteries is the relatively low capacity of cathode materials compared to anode materials. Owing to its high theoretical capacity, vanadium oxide is widely considered as an attractive cathode candidate. However, the main hindrances for its application in batteries are its poor capacity retention and low rate capability. Here, we report the development of multi-shelled vanadium oxide hollow microspheres and their related electrochemical properties. In contrast to the conventional cation-adsorption process, in which the metal cations adsorb on negatively charged carbonaceous templates, our approach enables the adsorption of metal anions. We demonstrate controlled syntheses of several multi-shelled metal oxide hollow microspheres. In particular, the multi-shelled vanadium oxide hollow microspheres deliver a specific capacity of 447.9 and 402.4mAhg(-1) for the first and 100th cycle at 1,000mAg(-1), respectively. The significant performance improvement offers the potential to reduce the wide capacity gap often seen between the cathode and anode materials.

Carrier-Free, Chemophotodynamic Dual Nanodrugs via Self-Assembly for Synergistic Antitumor Therapy

Abstract: There are tremendous challenges from both tumor and its therapeutic formulations affecting the effective treatment of tumor, including tumor recurrence, and complex multistep preparations of formulation. To address these issues, herein a simple and green approach based on the self-assembly of therapeutic agents including a photosensitizer (chlorine e6, Ce6) and a chemotherapeutic agent (doxorubicin, DOX) was developed to prepare carrier-free nanoparticles (NPs) with the ability to inhibit tumor recurrence. The designed NPs were formed by self-assembly of Ce6 and DOX associated with electrostatic, π–π stacking and hydrophobic interactions. They have a relatively uniform size of average 70 nm, surface charge of −20 mV and high drug encapsulation efficiency, which benefits the favorable accumulation of drugs at the tumor region through a potential enhanced permeability and retention (EPR) effect as compared to their counterpart of free Ce6 solution. In addition, they could eradiate tumors without recurrence ...

Biomimetic Immuno-Magnetosomes for High-Performance Enrichment of Circulating Tumor Cells.

Abstract: A novel biomimetic immuno-magnetosome (IMS) is developed by coating a leukocyte membrane (decorated with anti-epithelial cell-adhesion molecule antibody) on a magnetic nanocluster. In addition to the good stability and magnetic controllability, the IMS also exhibits satisfactory binding avidity to circulating tumor cells but stealth property to leukocytes. As a result, rare tumor cells can be effectively enriched with undetectable leukocyte background.

Interfacial Cohesion and Assembly of Bioadhesive Molecules for Design of Long-Term Stable Hydrophobic Nanodrugs toward Effective Anticancer Therapy

Abstract: The majority of anticancer drugs are poorly water-soluble and thus suffer from rather low bioavailability. Although a variety of delivery carriers have been developed for bioavailability improvement, they are severely limited by low drug loading and undesired side effects. The optimum delivery vehicle would be a biocompatible and biodegradable drug nanoparticle of uniform size with a thin but stable shell, making it soluble, preventing aggregation and enabling targeting. Here, we present a general strategy for the rational design of hydrophobic drug nanoparticles with high drug loading by means of interfacial cohesion and supramolecular assembly of bioadhesive species. We demonstrate that the pathway is capable of effectively suppressing and retarding Ostwald ripening, providing drug nanoparticles with small and uniform size and long-term colloidal stability. The final complex drug nanoparticles provide higher tumor accumulation, negligible toxicity, and enhanced antitumor activity, superior to commercial formulations. Our findings demonstrate that local, on-demand coating of hydrophobic nanoparticles is achievable through cooperation and compromise of interfacial adhesion and assembly.

Multitriggered Tumor-Responsive Drug Delivery Vehicles Based on Protein and Polypeptide Coassembly for Enhanced Photodynamic Tumor Ablation.

Abstract: Tumor-responsive nanocarriers are highly valuable and demanded for smart drug delivery particularly in the field of photodynamic therapy (PDT), where a quick release of photosensitizers in tumors is preferred. Herein, it is demonstrated that protein-based nanospheres, prepared by the electrostatic assembly of proteins and polypeptides with intermolecular disulfide cross-linking and surface polyethylene glycol coupling, can be used as versatile tumor-responsive drug delivery vehicles for effective PDT. These nanospheres are capable of encapsulation of various photosensitizers including Chlorin e6 (Ce6), protoporphyrin IX, and verteporfin. The Chlorin e6-encapsulated nanospheres (Ce6-Ns) are responsive to changes in pH, redox potential, and proteinase concentration, resulting in multitriggered rapid release of Ce6 in an environment mimicking tumor tissues. In vivo fluorescence imaging results indicate that Ce6-Ns selectively accumulate near tumors and the quick release of Ce6 from Ce6-Ns can be triggered by tumors. In tumors the fluorescence of released Ce6 from Ce6-Ns is observed at 0.5 h postinjection, while in normal tissues the fluorescence appeared at 12 h postinjection. Tumor ablation is demonstrated by in vivo PDT using Ce6-Ns and the biocompatibility of Ce6-Ns is evident from the histopathology imaging, confirming the enhanced in vivo PDT efficacy and the biocompatibility of the assembled drug delivery vehicles.

Co-Assembly of Graphene Oxide and Albumin/Photosensitizer Nanohybrids towards Enhanced Photodynamic Therapy

Abstract: The inactivation of photosensitizers before they reach the targeted tissues can be an important factor, which limits the efficacy of photodynamic therapy (PDT). Here, we developed co-assembled nanohybrids of graphene oxide (GO) and albumin/photosensitizer that have a potential for protecting the photosensitizers from the environment and releasing them in targeted sites, allowing for an enhanced PDT. The nanohybrids were prepared by loading the pre-assembled nanoparticles of chlorin e6 (Ce6) and bovine serum albumin (BSA) on GO via non-covalent interactions. The protection to Ce6 is evident from the inhibited fluorescence and singlet oxygen generation activities of Ce6–BSA–GO nanohybrids. Importantly, compared to free Ce6 and Ce6 directly loaded by GO (Ce6–GO), Ce6–BSA–GO nanohybrids showed enhanced cellular uptake and in vitro release of Ce6, leading to an improved PDT efficiency. These results indicate that the smart photosensitizer delivery system constructed by co-assembly of GO and albumin is promising to improve the stability, biocompatibility, and efficiency of PDT.

Co-Assembly of Heparin and Polypeptide Hybrid Nanoparticles for Biomimetic Delivery and Anti-Thrombus Therapy

Abstract: Biomimetic delivery carriers using polypeptide/heparin hybrid nanoparticles that are adsorbed onto red blood cells for extended blood circulation time have been developed. This might open up an avenue to promote the innovations and advances of biomimetic, stimuli-responsive drug delivery, especially for the site-specific treatment of intravascular diseases such as thrombosis.

Integration of Artificial Photosynthesis System for Enhanced Electronic Energy-Transfer Efficacy: A Case Study for Solar-Energy Driven Bioconversion of Carbon Dioxide to Methanol.

Abstract: Biocatalyzed artificial photosynthesis systems provide a promising strategy to store solar energy in a great variety of chemicals. However, the lack of direct interface between the light-capturing components and the oxidoreductase generally hinders the trafficking of the chemicals and photo-excited electrons into the active center of the redox biocatalysts. To address this problem, a completely integrated artificial photosynthesis system for enhanced electronic energy-transfer efficacy is reported by combining co-axial electrospinning/electrospray and layer-by-layer (LbL) self-assembly. The biocatalysis part including multiple oxidoreductases and coenzymes NAD(H) was in situ encapsulated inside the lumen polyelectrolyte-doped hollow nanofibers or microcapsules fabricated via co-axial electrospinning/electrospray; while the precise and spatial arrangement of the photocatalysis part, including electron mediator and photosensitizer for photo-regeneration of the coenzyme, was achieved by ion-exchange interaction-driven LbL self-assembly. The feasibility and advantages of this integrated artificial photosynthesis system is fully demonstrated by the catalyzed cascade reduction of CO2 to methanol by three dehydrogenases (formate, formaldehyde, and alcohol dehydrogenases), incorporating the photo-regeneration of NADH under visible-light irradiation. Compared to solution-based systems, the methanol yield increases from 35.6% to 90.6% using the integrated artificial photosynthesis. This work provides a novel platform for the efficient and sustained production of a broad range of chemicals and fuels from sunlight.

Pathogen-Mimicking Polymeric Nanoparticles based on Dopamine Polymerization as Vaccines Adjuvants Induce Robust Humoral and Cellular Immune Responses.

Abstract: Aiming to enhance the immunogenicity of subunit vaccines, a novel antigen delivery and adjuvant system based on dopamine polymerization on the surface of poly(D,L-lactic-glycolic-acid) nanoparticles (NPs) with multiple mechanisms of immunity enhancement is developed. The mussel-inspired biomimetic polydopamine (pD) not only serves as a coating to NPs but also functionalizes NP surfaces. The method is facile and mild including simple incubation of the preformed NPs in the weak alkaline dopamine solution, and incorporation of hepatitis B surface antigen and TLR9 agonist unmethylated cytosine-guanine (CpG) motif with the pD surface. The as-constructed NPs possess pathogen-mimicking manners owing to their size, shape, and surface molecular immune-activating properties given by CpG. The biocompatibility and biosafety of these pathogen-mimicking NPs are confirmed using bone marrow-derived dendritic cells. Pathogen-mimicking NPs hold great potential as vaccine delivery and adjuvant system due to their ability to: 1) enhance cytokine secretion and immune cell recruitment at the injection site; 2) significantly activate and maturate dendritic cells; 3) induce stronger humoral and cellular immune responses in vivo. Furthermore, this simple and versatile dopamine polymerization method can be applicable to endow NPs with characteristics to mimic pathogen structure and function, and manipulate NPs for the generation of efficacious vaccine adjuvants.

Castor oil‐based waterborne polyurethanes with tunable properties and excellent biocompatibility

Abstract: Biopolymers materials with tunable properties are the spotlight in the polymer molecules design and synthesis. Here, we synthesize a series of castor oil based‐waterborne polyurethanes (CWPUs) with highly tunable properties by adjusting the content of 2,2‐dimethylolbutanoic acid (DMBA), a hydrophilic chain extender. The size of the polyurethane dispersions (PUDs) decreases from 120 nm to 20 nm, when DMBA content increases from 5 to 9 wt%. Infrared spectrum of the corresponding CWPUs films shows that the hydrogen bonds between hard segments have an enhancement as DMBA content increases. The thermal and mechanical properties of the CWPUs films have an obvious change due to this enhanced hydrogen bond interactions and behave like soft elastomer or rigid plastic. For example, the glass transition temperature (Tg) of the CWPUs films increases from 47.8 to 92.9 °C and meanwhile the tensile strength increases from 9.6 to 20.0 MPa. In addition, the CWPUs films are enzymatically hydrolysable due to the surface hydrophilicity. Importantly, those films exhibit excellent biocompatibility to mouse fibroblast (L‐929) cells and a relative cell viability of 76% compared to tissue culture polystyrene (TCPS) plates is obtained. Practical applications: The synthesized CWPUs are versatile by change of the content of DMBA. The CWPUs can potentially replace wide range of part of petroleum‐based polymeric materials. In view of their good biodegradability and biocompatibility, the CWPUs are promising in biomedical applications. Castor oil‐based waterborne polyurethanes show highly tunable properties and excellent biocompatibility, which are promising in on‐demand biomedical applications.

Molecular and Mesoscale Mechanism for Hierarchical Self-Assembly of Dipeptide and Porphyrin Light-Harvesting System

Abstract: A multi-scale theoretical investigation of dipeptide–porphyrin co-assembly systems has been carried out to establish such understanding, where two different types of the dipeptides, dilysine (KK3+) and diphenylalanine (FF+) are compared on tuning the porphyrin organization. Density functional theory results reveal that the electrostatic attraction between different functional groups has significantly strengthened the hydrogen bonds between them, which are considered as the driving force of the self-assembly at the molecular level. All-atom molecular dynamics (MD) simulation further indicates that the formation of the core–shell nanorods is driven and stabilized by the hydrophobic interaction between dipeptides and negatively charged porphyrin (H2TPPS2−), where the packed porphyrins stay inside as the core of the nanorods and the hydrophilic groups (amino- and carboxyl-groups) as the shell. With stronger hydrophobicity, FF+ is more likely to insert into the porphyrin aggregates and build crosslinks than KK3+. Moreover, dissipative particle dynamics (DPD) simulation suggests equilibrium morphologies with different dipeptides, where KK3+–H2TPPS2− assembled in fiber bundles, whereas FF+–H2TPPS2− assembled as microspheres, corresponding to the different packing behavior in MD simulations. The consistency of these results at different scales is discussed. The method used in this work could be extended for studying similar issues in hierarchical self-assembly of building blocks such biomaterials.

TiO2–Horseradish Peroxidase Hybrid Catalyst Based on Hollow Nanofibers for Simultaneous Photochemical–Enzymatic Degradation of 2,4-Dichlorophenol

Abstract: Degradations of 2,4-dichlorophenol (2,4-DCP) using TiO2/UV photochemical and horseradish peroxidase (HRP) enzymatic treatments, as well as simultaneous photochemical–enzymatic treatments, by combining these two processes were systematically investigated and compared. When free HRP was used in the simultaneous process, a negative synergetic effect was observed due to serious inactivation of the HRP caused by UV irradiation in the presence of TiO2. A hybrid catalyst system was then developed by in situ encapsulating HRP inside nanochambers of TiO2-doped hollow nanofibers through coaxial electrospinning. Such encapsulation effectively avoided UV-induced deactivation of the enzymes, thus the 2,4-DCP degradation efficiency was improved significantly as compared with the that using HRP or TiO2/UV either separately or simultaneously in free formation. Furthermore, the higher the concentration of 2,4-DCP, the more remarkable the enhancement achieved, such that a 90% removal ratio was obtained within only 3 h for ...

Regulating Cell Apoptosis on Layer-by-Layer Assembled Multilayers of Photosensitizer-Coupled Polypeptides and Gold Nanoparticles.

Abstract: The design of advanced, nanostructured materials by layer-by-layer (LbL) assembly at the molecular level is of great interest because of the broad application of these materials in the biomedical field especially in regulating cell growth, adhesion, movement, differentiation and detachment. Here, we fabricated functional hybrid multilayer films by LbL assembly of biocompatible photosensitizer-coupled polypeptides and collagen-capped gold nanoparticles. The resulting multilayer film can well accommodate cells for adhesion, growth and proliferation. Most significantly, controlled cell apoptosis (detachment) and patterning of the multilayer film is achieved by a photochemical process yielding reactive oxygen species (ROS). Moreover, the site and shape of apoptotic cells can be controlled easily by adjusting the location and shape of the laser beam. The LbL assembled multilayer film with integration of functions provides an efficient platform for regulating cell growth and apoptosis (detachment).

Covalent immobilization of trypsin onto thermo-sensitive poly(N-isopropylacrylamide-co-acrylic acid) microspheres with high activity and stability

Abstract: Poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAM-co-AA)) microspheres with a high copolymerized AA content were fabricated using rapid membrane emulsification technique. The uniform size, good hydrophilicity, and thermo sensitivity of the microspheres were favorable for trypsin immobilization. Trypsin molecules were immobilized onto the microspheres surfaces by covalent attachment. The effects of various parameters such as immobilization pH value, enzyme concentration, concentration of buffer solution, and immobilization time on protein loading amount and enzyme activity were systematically investigated. Under the optimum conditions, the protein loading was 493 +/- 20 mgg(-1) and the activity yield of immobilized trypsin was 155%+/- 3%. The maximum activity (V-max) and Michaelis constant (K-m) of immobilized enzyme were found to be 0.74 Ms-1 and 0.54 mM, respectively. The immobilized trypsin showed better thermal and storage stability than the free trypsin. The enzyme-immobilized microspheres with high protein loading amount still can show a thermo reversible phase transition behavior. The research could provide a strategy to immobilize enzyme for application in proteomics. (c) 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43343.

Breaching the Hyaluronan Barrier with PH20-Fc Facilitates Intratumoral Permeation and Enhances Antitumor Efficiency: A Comparative Investigation of Typical Therapeutic Agents in Different Nanoscales.

Abstract: In contrast to traditional strategies based on external driving forces, an internal path for intratumoral delivery is explored by degrading the tumor microenvironment component hyaluronan. Natural hyaluronidase PH20 and constructed long-acting PH20-Fc have been used to achieve this objective. It has been then evaluated how these agents facilitate the diffusion of the following typical therapeutic agents varying in nanoscales: doxorubicin (≈1.5 × 1.0 × 0.7 nm) chemotherapy, trastuzumab (10-15 nm) biotherapy, and gold nanorod (≈100 × 35 nm) thermotherapy. In traditional 2D cultures, PH20 and PH20-Fc have little influence on cytotoxicity due to lack of a tumor microenvironment. However, the cytotoxicities of the three therapeutic agents in 3D tumor spheroids are all enhanced by PH20 or PH20-Fc because hyaluronan degradation facilitates therapeutic penetration and accumulation. Furthermore, in vivo evaluations reveal that the significantly prolonged circulation time of PH20-Fc leads to accumulation in the tumor and subsequent hyaluronan degradation. Consequently, PH20-Fc coadministration further inhibits tumor growth. The performance of PH20-Fc varies for the three therapeutic agents due to their different nanoscales. Trastuzumab benefits most from combination with PH20-Fc. The results provide here novel insights that can aid in the development of more effective hyaluronidase-based therapeutic systems.

Microenvironment-Responsive Three-Pronged Approach Breaking Traditional Chemotherapy to Target Cancer Stem Cells for Synergistic Inoperable Large Tumor Therapy

Abstract: Three-pronged nanoparticles (NPs) that can efficiently prohibit the proliferation of large tumor are developed for inoperable large tumor therapy. The NPs achieve spatially and temporally controlled release of drugs in target sites. The NPs induce the apoptosis of differentiated cancer cells, cancer stem cells, and vascular niches simultaneously. Importantly, the three-pronged NPs inhibit the growth of large tumors without recurrence.

Cell-nanoparticle assembly fabricated for CO2 capture and in situ carbon conversion

Abstract: Some microorganisms can selectively capture carbon dioxide without light irradiation, which proposes a wide application prospect. The purpose of this study was to create a microorganism-nanoparticle assembly, which will be used for carbon dioxide fixation and in situ conversion into a platform chemical, succinic acid. Firstly, uniform size-controlled magnetic nanomaterial were synthesized and well assembled with non-photosynthetic carbon-fixation microorganism Actinobacillus succinogenes 130Z. CO2 capture efficiency can be improved dramatically by enhancing the transfer of carbon dioxide between gas phase and cytoplasm by the hydrophilic oleate-modified Fe3O4 nanoparticles. The assembly will integrate the advantages of two processes, carbon dioxide sequestration by cells and carbon dioxide adsorption by chemical reagents, which resulted in 71 mmol CO2 fixation/g dry cell in 24 h. This article provides a basic study for CO2 sequestration and carbon resource utilization. (C) 2015 Elsevier Ltd. All rights reserved.

Corrigendum: Multi-shelled metal oxides prepared via an anion-adsorption mechanism for lithium-ion batteries

Abstract: Nature Energy 1, 16050 (2016); published 29 April 2016; corrected 11 May 2016. In the version of this Article originally published the numbering of the author affiliations was incorrect.

Improved Stability of Emulsions in Preparation of Uniform Small-Sized Konjac Glucomanna (KGM) Microspheres with Epoxy-Based Polymer Membrane by Premix Membrane Emulsification.

Abstract: Uniform small-sized (<10 μm) Konjac glucomanna (KGM) microspheres have great application prospects in bio-separation, drug delivery and controlled release. Premix membrane emulsification is an effective method to prepare uniform small-sized KGM microspheres. However, since KGM solution bears strong alkalinity, it requires the membrane to have a hydrophobic surface resistant to alkali. In this study, uniform small-sized KGM microspheres were prepared with epoxy-based polymer membrane (EP) we developed by premix membrane emulsification. It was found that emulsion coalescence and flocculation occurred frequently due to the high interface energy and sedimentation velocity of KGM emulsions. Emulsion stability had a significant influence on the uniformity and dispersity of the final KGM microspheres. To improve the stability of the emulsions, the effects of the concentration of the emulsifier, the viscosity of the KGM solution, the oil phase composition and the feeding method of epoxy chloropropane (EC) on the preparation results were studied. Under optimal preparation conditions (emulsifier 5 wt % PO-5s, KGM III (145.6 mPa·s), weight ratio of liquid paraffin (LP) to petroleum ether (PE) 11:1), uniform and stable KGM emulsions (d = 7.47 μm, CV = 15.35%) were obtained and crosslinked without emulsion-instable phenomena.