16 research outputs found

    Protein-Cross-Linked Hydrogels with Tailored Swelling and Bioactivity Performance: A Comparative Study

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    The design of protein-based hydrogels that include biological activity independent of structural functionality is desirable for many bioengineering applications. Here a general route for construction of protein-based hydrogel is proposed by pretreatment of protein with thiolation agent and succeeding conjugation with 4-arm PEG-acrylate via Michael addition reaction. Different swelling behaviors responding to temperature and ions are comparatively studied for hydrogel cross-linked with hemoglobin (multimeric protein), albumin (monomeric protein), and dithiothreitol (DTT, small molecule). Meanwhile, the microscopic structure change is studied to correlate with the macroscopic hydrogel swelling behavior. Results show that proteins, which function as multisite cross-linkers, affect the gel swelling behaviors, and the effect is more profound for multimeric proteins when exposed to stimulus for protein dissociation. Moreover, the catalytic activity derived from hemoglobin is also preserved in the hydrogel, as demonstrated by the successfully synthesis of the colored product. By taking advantage of each particular protein, a broad range of functional materials can be expected for potential biomedical applications, such as stimuli-responsive hydrogel and immobilized enzyme

    Protein-Cross-Linked Hydrogels with Tailored Swelling and Bioactivity Performance: A Comparative Study

    No full text
    The design of protein-based hydrogels that include biological activity independent of structural functionality is desirable for many bioengineering applications. Here a general route for construction of protein-based hydrogel is proposed by pretreatment of protein with thiolation agent and succeeding conjugation with 4-arm PEG-acrylate via Michael addition reaction. Different swelling behaviors responding to temperature and ions are comparatively studied for hydrogel cross-linked with hemoglobin (multimeric protein), albumin (monomeric protein), and dithiothreitol (DTT, small molecule). Meanwhile, the microscopic structure change is studied to correlate with the macroscopic hydrogel swelling behavior. Results show that proteins, which function as multisite cross-linkers, affect the gel swelling behaviors, and the effect is more profound for multimeric proteins when exposed to stimulus for protein dissociation. Moreover, the catalytic activity derived from hemoglobin is also preserved in the hydrogel, as demonstrated by the successfully synthesis of the colored product. By taking advantage of each particular protein, a broad range of functional materials can be expected for potential biomedical applications, such as stimuli-responsive hydrogel and immobilized enzyme

    Protein-Cross-Linked Hydrogels with Tailored Swelling and Bioactivity Performance: A Comparative Study

    No full text
    The design of protein-based hydrogels that include biological activity independent of structural functionality is desirable for many bioengineering applications. Here a general route for construction of protein-based hydrogel is proposed by pretreatment of protein with thiolation agent and succeeding conjugation with 4-arm PEG-acrylate via Michael addition reaction. Different swelling behaviors responding to temperature and ions are comparatively studied for hydrogel cross-linked with hemoglobin (multimeric protein), albumin (monomeric protein), and dithiothreitol (DTT, small molecule). Meanwhile, the microscopic structure change is studied to correlate with the macroscopic hydrogel swelling behavior. Results show that proteins, which function as multisite cross-linkers, affect the gel swelling behaviors, and the effect is more profound for multimeric proteins when exposed to stimulus for protein dissociation. Moreover, the catalytic activity derived from hemoglobin is also preserved in the hydrogel, as demonstrated by the successfully synthesis of the colored product. By taking advantage of each particular protein, a broad range of functional materials can be expected for potential biomedical applications, such as stimuli-responsive hydrogel and immobilized enzyme

    Blends of Linear and Long-Chain Branched Poly(l‑lactide)s with High Melt Strength and Fast Crystallization Rate

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    The long-chain branched polylactides (LCB-PLAs) prepared by coupling the hydroxyl-terminated two-arm (linear) and triarm PLA prepolymers of identical arm length with hexamethylenediacianate (HDI) were used to improve the melt rheological and crystallization properties of linear polylactide resin, PLA 4032D from NatureWorks. The blends containing LCB-PLA displayed higher zero shear viscosities, more significant shear shinning, more melt elasticity, and much longer relaxation times together with significant strain hardening in elongational deformation. <i>T</i><sub>g</sub>, <i>T</i><sub>m</sub> and crystallinity (<i>X</i><sub>c</sub>) of linear PLA remained virtually unaffected, but the crystallization rate increased obviously, since the branch points of LCB-PLAs could play a role of nucleating agent. High melt strength, fast crystallization, and favorable miscibility improved the foaming ability of the linear/LCB-PLA blends, substantially

    Biodegradable Amphiphilic Copolymer Containing Nucleobase: Synthesis, Self-Assembly in Aqueous Solutions, and Potential Use in Controlled Drug Delivery

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    Biodegradable nucleobase-grafted amphiphilic copolymer, the methoxyl poly (ethylene glycol)-<i>b</i>-poly (L-lactide-<i>co</i>-2-methyl-2­(3-(2,3-dihydroxylpropylthio) propyloxycarbonyl)-propylene carbonate/1-carboxymethylthymine) (mPEG-<i>b</i>- P­(LA-<i>co</i>-MPT)), was synthesized. <sup>1</sup>H NMR titration and FT-IR spectroscopy indicated that the hydrogen-bonding could be formed between mPEG-<i>b</i>-P­(LA-<i>co</i>-MPT) and 9-hexadecyladenine (A-C16). The hydrophobic microenvironment of the amphiphilic copolymer can protect the complementary multiple hydrogen bonds between mPEG-<i>b</i>-P­(LA-<i>co</i>-MPT) and A-C16 from water effectively. The addition of A-C16 not only lowered the critical aggregation concentration (CAC) of mPEG-<i>b</i>-P­(LA-<i>co</i>-MPT)/A-C16 nanoparticles (NPs) in aqueous solution but also induced different morphologies, which can be observed by transmission electron microscopy (TEM). Meanwhile, dynamic light scattering (DLS) and turbidometry was utilized to evaluate the effect of temperature and pH change on the stability of mPEG-<i>b</i>-P­(LA-<i>co</i>-MPT)/A-C16 NPs. Cytotoxicity evaluation showed good biocompatibility of the mPEG-<i>b</i>-P­(LA-<i>co</i>-MPT)/A-C16 NPs. The <i>in vitro</i> drug release profile showed that with the increase of A-C16 content, the doxorubiucin (DOX) release at pH 7.4 decreased, while the faster release rate was observed with the addition of A-C16 with a pH of 5.0. Importantly, DOX-loaded NPs exerted comparable cytotoxicity against MDA-MB-231 cells. This work provided a new method to stabilize NP structure using hydrogen-bonds and would have the potential to be applied in controlled drug delivery

    Transferrin-Conjugated Micelles: Enhanced Accumulation and Antitumor Effect for Transferrin-Receptor-Overexpressing Cancer Models

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    As the transport protein for iron, transferrin can trigger cellular endocytosis once binding to its receptor (TfR) on the cell membrane. Using this property, we conjugated transferrin onto the surface of biodegradable polymeric micelles constructed from amphiphilic block copolymers. The core of micelle was either labeled with a near-infrared dye (NIR) or conjugated with a chemotherapeutic drug paclitaxel (PTX) to study the biodistribution or antitumor effect in nude mice bearing subcutaneous TfR-overexpressing cancers. DLS and TEM showed that the sizes of Tf-conjugated and Tf-free micelles were in the range of 85–110 nm. Confocal laser scanning microscopy and flow cytometry experiments indicated that the uptake efficiency of the micelles by the TfR-overexpressing cells was enhanced by Tf conjugation. Semiquantitative analysis of the NIR signals collected from the tumor site showed that the maximum accumulation was achieved at 28 h in the M­(NIR) group, while at 22 h in Tf–M­(NIR) groups; and the area under the intensity curve in the Tf–M­(NIR) groups was more than that in M­(NIR) group. Finally, the tumor inhibition effects of targeting micelles were studied with the gastric carcinoma model which overexpressed TfR. The analysis of tumor volumes and the observation of H&E-stained tumor sections showed that Tf–M­(PTX) had the best antitumor effect compared with the control groups (saline, PTX, and M­(PTX)). The results of this study demonstrated the potential application of Tf-conjugated polymeric micelles in the treatment of TfR-overexpressing cancers

    Enhancing Therapeutic Efficacy of Cisplatin by Blocking DNA Damage Repair

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    Self-repair of nuclear DNA damage is the most known reason that leads to drug resistance of cancer tissue and limited therapeutic efficacy of anticancer drugs. Inhibition of protein phosphatase 2A (PP2A) would block DNA damage-induced defense of cancer cells to suppress DNA repair for enhanced cancer treatment. Here, we combined a PP2A inhibitor LB (4-(3-carboxy-7-oxa-bicyclo[2.2.1]­heptane-2-carbonyl) piperazine-1-carboxylic acid <i>tert</i>-butyl ester) and the DNA damage chemotherapeutic drug cisplatin through a simple physical superposition. The two drugs administrated at a ratio of 1:1 exhibited an optional synergistic antitumor efficacy <i>in vitro</i> and <i>in vivo</i>. LB was demonstrated to specifically activate the protein kinase B (Akt) and mitogen-activated protein kinases (MAPK) signaling pathways by PP2A inhibition to overcome cell cycle arrest caused by cisplatin-induced DNA damage

    Compact Vesicles Self-Assembled from Binary Graft Copolymers with High Hydrophilic Fraction for Potential Drug/Protein Delivery

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    Hollow vesicles self-assembled from amphiphilic copolymers are of great interest in biomedicine field as drug and protein carriers. Efficient preparation of polymeric vesicles with high stability in vivo is highly desirable. Herein, a novel cooperative self-assembly of two graft copolymers (GCPs) with reversed hydrophilic–hydrophobic segments is investigated to achieve morphology control for biomedical application. Interestingly, nanosized vesicles are obtained for the binary system with relatively high hydrophilic fraction (<i>f</i><sub>hydrophilic</sub>, ∌60%), contrary to what is found in its single-component counterpart. The cooperative self-assembly endowed the hybrid vesicles with excellent resistance to protein adsorption, prolonged blood circulation time, as well as low leakage of hydrophilic drugs/proteins. Furthermore, the biological activity of the protein is well preserved inside the cooperative vesicles, making it a promising candidate as the protein carrier

    Layer-by-Layer Assembled Polypeptide Capsules for Platinum-Based Pro-Drug Delivery

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    Platinum­(IV), a pro-drug of platinum­(II), was conjugated to poly­(l-lysine) (PLL), and then assembled with poly­(glutamic acid) (PGA) through a layer-by-layer (LbL) approach on colloidal silica templates. After removal of the templates, biodegradable PGA/PLL-Pt­(IV) multilayer capsules (diameter = 0.5 Όm) with 10 Όg of platinum incorporated into each bilayer were obtained. Under acidic and/or reductive conditions, the amount and rate of platinum released from the capsules were increased, which are desirable traits for platinum-based anticancer drug delivery systems. Furthermore, in vitro evaluation showed that the PGA/PLL-Pt­(IV) multilayer microcapsules displayed higher cytotoxicity (IC<sub>50Pt</sub> = 3.5 Όg/mL) against colon cancer cells CT-26 than that of free cisplatin (IC<sub>50Pt</sub> = 8.6 Όg/mL). This enhanced cytotoxicity was attributed to the effective internalization of the capsules by the cancer cells, which was observed by confocal laser scanning microscopy (CLSM) imaging
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