The performance of many therapeutic proteins, including human interferon-α2b (IFN), is often impeded by their intrinsic instability to protease, poor pharmacokinetics, and strong immunity. Although PEGylation has been an effective approach to improve the pharmacokinetics of many proteins, a few noticeable limitations have aroused vast research efforts in seeking alternatives to PEG for bioconjugation. Herein, we report our investigation on the use of polysarcosine (PSar), a nonionic and hydrophilic polypeptoid, for IFN modification. The site-specific conjugate PSar-IFN, generated by native chemical ligation in high yield, is systematically compared with a similarly produced PEG-interferon conjugate (PEG-IFN) to evaluate the in vitro and in vivo behaviors. PSar is found to show comparable ability in stabilizing IFN from protease digestion in vitro and prolonging the circulation half-life in vivo. Interestingly, PSar-IFN retains more activity in vitro and accumulates more in the tumor sites upon systemic administration than PEG-IFN. Most importantly, PSar-IFN is significantly more potent in inhibiting tumor growth and elicits considerably less anti-IFN antibodies in mouse than PEG-IFN. Together, our results demonstrate for the first time that PSar is an outstanding candidate for therapeutic protein conjugation. Considering the low toxicity, biodegradability, and excellent stealth effect of PSar, this study suggests that such polypeptoids hold enormous potential for many biomedical applications including protein delivery, colloidal stabilization, and nanomedicine.

Large-scale well-aligned ZnO nanotubes with outer diameters of 100-300 nm and lengths of tens of micrometres have been prepared by a template-based chemical vapour deposition method. The photoluminescence spectrum of the ZnO nanotube arrays consists of a strong violet band at 414 nm, a blue band at 462 nm and a weak shoulder peak at around 480 nm. The field emission of the ZnO nanotube arrays shows a turn-on field of about 7.3 V microm(-1) at a current density of 0.1 microA cm(-2) and emission current density up to 1.3 mA cm(-2) at a bias field of 11.8 V microm(-1).

A convenient method for the direct and large-area growth of one-dimensional (1-D) ZnO nanostructures on a conductive brass substrate has been developed, consisting of thermal oxidation of a Cu 0.66 Zn 0.34 alloy foil in the presence of oxygen. Various 1-D nanostructures such as nanowires, nanobelts, nanocombs, and nanosheets have been in situ grown on the brass substrate under different reaction temperatures and characterized by means of X-ray diffraction, electron microscopy, and X-ray photoelectron spectroscopy. In this preparation, the Cu 0.66 Zn 0.34 alloy foil functions as both Zn source and substrate for the growth of 1-D ZnO nanostructures; thus, the synthesis and assembly of ZnO nanostructures on a metallic substrate is accomplished in one step, and the naturally good adhesion or electrical connection between the ZnO nanostructures and the conductive substrate has been realized. This approach could prepare ZnO nanostructures on a brass substrate without size limitations. Such a configuration of product is a good field emitter as demonstrated in this study. The potential technological importance of the product, the simplicity of the preparation procedure, as well as the cheap commercial precursor of the Cu 0.66 Zn 0.34 alloy foil makes this study both scientifically and technologically interesting.

Polymer conjugation is a clinically proven approach to generate long acting protein drugs with decreased immune responses. Although poly(ethylene glycol) (PEG) is one of the most commonly used conjugation partners due to its unstructured conformation, its therapeutic application is limited by its poor biodegradability, propensity to induce an anti-PEG immune response, and the resultant accelerated blood clearance (ABC) effect. Moreover, the prevailing preference of unstructured polymers for protein conjugation still lacks strong animal data support with appropriate control reagents. By using two biodegradable synthetic polypeptides with similar structural compositions ( l -P(EG 3 Glu) and dl -P(EG 3 Glu)) for site-specific protein modification, in the current study, we systematically investigate the effect of the polymer conformation on the in vivo pharmacological performances of the resulting conjugates. Our results reveal that the conjugate l 20K -IFN, interferon (IFN) modified with the helical polypeptide l -P(EG 3 Glu) shows improved binding affinity, in vitro antiproliferative activity, and in vivo efficacy compared to those modified with the unstructured polypeptide analogue dl -P(EG 3 Glu) or PEG. Moreover, l 20K -IFN triggered significantly less antidrug and antipolymer antibodies than the other two. Importantly, the unusual findings observed in the IFN series are reproduced in a human growth hormone (GH) conjugate series. Subcutaneously infused l 20K -GH, GH modified with l -P(EG 3 Glu), evokes considerably less anti-GH and antipolymer antibodies compared to those modified with dl -P(EG 3 Glu) or PEG ( dl 20K -GH or PEG 20K –GH). As a result, repeated injections of dl 20K -GH or PEG 20K -GH, but not l 20K -GH, result in a clear ABC effect and significantly diminished drug availability in the blood. Meanwhile, immature mouse bone marrow cells incubated with the helical l 20K -GH exhibit decreased drug uptake and secretion of proinflammatory cytokines compared to those treated with one of the other two GH conjugates bearing unstructured polymers. Taken together, the current study highlights an urgent necessity to systematically reassess the pros and cons of choosing unstructured polymers for protein conjugation. Furthermore, our results also lay the foundation for the development of next-generation biohybrid drugs based on helical synthetic polypeptides.

A simple chemical method for the production of single-crystalline alpha-Si(3)N(4) nanobelts has been developed, consisting of nitridation of a high-Si-content Fe-Si 'catalyst' by ammonia at 1300 degrees C. The as-synthesized product was characterized by means of x-ray diffraction, electron microscopy and energy-dispersive x-ray spectroscopy. The alpha-Si(3)N(4) nanobelts have widths of 60-120 nm, thicknesses of 10-30 nm and lengths up to microns. Four intense green-blue luminescence bands at 398 nm (3.12 eV), 434 nm (2.86 eV), 492 nm (2.52 eV) and 540 nm (2.30 eV) were observed and analysed for the product, which indicates the potential applications in optoelectronics. The growth mechanism has also been speculated upon. The potential technological importance of the product, the simplicity of the preparation procedure, as well as the cheap commercial precursor of Fe-Si alloy particles makes this study both scientifically and technologically interesting.

Highly oriented SiC porous nanowire (NW) arrays on Si substrate have been achieved via in situ carbonizing aligned Si NW arrays standing on Si substrate. The resultant SiC NW arrays inherit the diameter and length of the mother Si NW arrays. Field emission measurements show that these oriented SiC porous NW arrays are excellent field emitter with large field emission current denstity at very low electric field. The in situ conversion method reported here might be exploited to fabricate NW arrays of other materials containing silicon.

Cyclization and polymer conjugation are two commonly used approaches for enhancing the pharmacological properties of protein drugs. However, cyclization of parental proteins often only affords a modest improvement in biochemical or cell-based in vitro assays. Moreover, very few studies have included a systematic pharmacological evaluation of cyclized protein-based therapeutics in live animals. On the other hand, polymer-conjugated proteins have longer circulation half-lives but usually show poor tumor penetration and suboptimal pharmacodynamics due to increased steric hindrance. We herein report the generation of a head-to-tail interferon-poly(α-amino acid) macrocycle conjugate circ-P(EGGlu)-IFN by combining the aforementioned two approaches. We then compared the antitumor pharmacological activity of this macrocycle conjugate against its linear counterparts, N-P(EGGlu)-IFN, C-IFN-P(EGGlu), and C-IFN-PEG. Our results found circ-P(EGGlu)-IFN to show considerably greater stability, binding affinity, and in vitro antiproliferative activity toward OVCAR3 cells than the three linear conjugates. More importantly, circ-P(EGGlu)-IFN exhibited longer circulation half-life, remarkably higher tumor retention, and deeper tumor penetration in vivo. As a result, administration of the macrocyclic conjugate could effectively inhibit tumor progression and extend survival in mice bearing established xenograft human OVCAR3 or SKOV3 tumors without causing severe paraneoplastic syndromes. Taken together, our study provided until now the most relevant experimental evidence in strong support of the in vivo benefit of macrocyclization of protein-polymer conjugates and for its application in next-generation therapeutics.

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