Systematic and Quantitative Structure-Property Relationships of Polymeric Medical Nanomaterials: From Systematic Synthesis and Characterization to Computer Modeling and Nano-Bio Interaction and Toxicity.

Nanomaterials allow designing targeted therapies, facilitate molecular diagnostics, and are therefore enabling platforms for personalized medicine. A systematic science and a predictive understanding of molecular/supramolecular structure relationships and nanoparticle structure/biological property relationships are needed for rational design and clinical progress but are hampered by the anecdotal nature, nonsystematic and nonrepresentative nanomaterial assortment, and oligo-disciplinary approach of many publications. Here, we find that a systematic and comprehensive multidisciplinary approach to production and exploration of molecular-structure/nanostructure relationship and nano-bio structure/function relationship of medical nanomaterials can be achieved by combining systematic chemical synthesis, thorough physicochemical analysis, computer modeling, and biological experiments, as shown in a nanomaterial family of amphiphilic, micelle-forming oxazoline/siloxane block copolymers suited for the clinical application.

FRET in a Polymeric Nanocarrier: IR-780 and IR-780-PDMS.

We introduce a method to monitor the integrity of micellar nanocarriers using a novel fluorescent dye, IR-780-PDMS and Förster resonance energy transfer (FRET) as a readout. In addition, these dye-loaded nanocarriers can be used as a phototoxic agent in vitro. Mainly, a nanocarrier was designed, based on a previously described amphiphilic ABA-copolymer (Pip-PMOXA-PDMS-PMOXA-Pip) scaffold that incorporates the fluorescent FRET dye partners IR-780-PDMS (donor) and IR-780 (acceptor).

Efficient Receptor Mediated siRNA Delivery in Vitro by Folic Acid Targeted Pentablock Copolymer-Based Micelleplexes.

Novel, biocompatible polyplexes, based on the combination of cationic pentablock copolymers with folic acid functionalized copolymers, were designed and developed for target-specific siRNA delivery. The resulting micelleplexes spontaneously formed polymeric micelles with a hydrophobic core surrounded directly by a cationic poly-2-(4-aminobutyl)-oxazole (PABOXA) and subsequently shielded by hydrophilic poly-2-methyl-oxazole (PMOXA) layer. The described micelleplexes form highly stable particles even in complete serum after 24 h compared with the highly cationic polymer PEI, which show aggregate formation in serum containing buffer solution.

A comparison of plasmid DNA delivery efficiency and cytotoxicity of two cationic diblock polyoxazoline copolymers.

Cationic polymers as non-viral gene delivery carriers are widely used because of their strong condensing properties and long-term safety, but acute cytotoxicity is a persistent challenge. In this study, two types of polyplexes were prepared by co-formulating plasmid DNA and two cationic diblock copolymers PABOXA-b-PMOXA-PA (primary amine) and PABOXA-b-PMOXA-TA (tertiary amine) to check their transfection efficacies in HeLa cells and HEK293T cells, respectively. The plasmid DNA/PABOXA-b-PMOXA-PA polyplex showed higher transfection efficacy compared to the plasmid DNA/PABOXA-b-PMOXA-TA polyplex under an N/P ratio of 40.

A Versatile Bonding Method for PDMS and SU-8 and Its Application towards a Multifunctional Microfluidic Device.

This paper reports a versatile and irreversible bonding method for poly(dimethylsiloxane) (PDMS) and SU-8. The method is based on epoxide opening and dehydration reactions between surface-modified PDMS and SU-8. A PDMS replica is first activated via the low-cost lab equipment, i.

Carbohydrate-based amphiphilic nano delivery systems for cancer therapy.

Nanoparticles (NPs) are novel drug delivery systems that have been attracting more and more attention in recent years, and have been used for the treatment of cancer, infection, inflammation and other diseases. Among the numerous classes of materials employed for constructing NPs, organic polymers are outstanding due to the flexibility of design and synthesis and the ease of modification and functionalization. In particular, NP based amphiphilic polymers make a great contribution to the delivery of poorly-water soluble drugs.

Microfluidics-based single-step preparation of injection-ready polymeric nanosystems for medical imaging and drug delivery.

Translation of therapeutic polymeric nanosystems to patients and industry requires simplified, reproducible and scalable methods for assembly and loading. A single-step in-line process based on nanocoprecipitation of oxazoline-siloxane block copolymers in flow-focusing poly(dimethylsiloxane) microfluidics was designed to manufacture injection-ready nanosystems. Nanosystem characteristics could be controlled by copolymer concentration, block length and chemistry, microchannel geometry, flow rate, aqueous/organic flow rate ratio and payload concentration.

[Regional difference of schistosomiasis knowledge and behavior of population in Mianzhu City].

Objective: To understand the status of schistosomiasis knowledge and behavior and analyze the regional difference of population in Mianzhu City.

Methods: Nine towns were divided into 3 groups, and each group had 3 towns. In Group I , there were 5 or more than 5 advanced schistosomiasis patients each town; in Group II , there were 1-4 advanced patients each town; in Group III, there was no advanced patient.

[Surveillance of schistosomiasis of reconstruction personnel after earthquake in Mianzhu City from 2009 to 2011].

After "5.12" earthquake, 5 128 reconstruction people from schistosomiasis endemic areas were surveyed for schistosome infection from 2009 to 2001. There were 261 seropositive persons with the positive rate of 5.

Asymmetric synthesis and biological activity of nor-α-tocopherol, a new vitamin E analogue.

The vitamin E analogues (2R,4'R,8'R)-nor-α-tocopherol (94 % de) and (2RS,4'R,8'R)-nor-α-tocopherol have been synthesized from (all R)-hexahydrofarnesol and phytol, respectively. According to in vitro experiments with murine macrophages nor-α-tocopherol is an anti-inflammatory compound more potent than α-tocopherol.

Recent biomimetic and organocatalytic syntheses of alpha-tocopherol.

We report here on our efforts to develop new strategies for the synthesis of alpha-tocopherol, the biologically most significant member of the vitamin E family. This review comprises five new methods to generate the chiral chromane of alpha-tocopherol with overall up to 29% yield from commercially available material and up to 94% de.

Asymmetric synthesis of alpha-tocopherol.

Alpha-tocopherol was synthesized from a chiral intermediate alpha-hydroxy ester by means of two ring-closing methods to yield the chromanol in 94% diastereomeric excess.

Solid-phase oligosaccharide synthesis of a small library of N-glycans.

Solid-phase oligosaccharide synthesis is based on a hydroxymethylbenzyl benzoate spacer linker which is connected to the Merrifield resin (1 P). Glycosylation was performed with O-glycosyl trichloroacetimidates of glucosamine, mannose, and galactose permitting chain extension (2e, 5e), branching (4b, 7b, 8b), and chain termination (3t, 6t, 9t) with the use of O-benzyl, O-benzoyl, and N-dimethylmaleoyl as permanent and O-fluorenylmethoxycarbonyl (Fmoc) and O-phenoxyacetyl (PA) as temporary protecting groups. The steps required on solid phase are i) glycosylation under TMSOTf catalysis, ii) selective cleavage of the temporary protecting groups, Fmoc with NEt3 and PA with 0.

Chemoselective deprotection of cyclic N,O-aminals using catalytic bismuth(III) bromide in acetonitrile.

Cyclic N,O-aminals can be chemoselectively and efficiently deprotected using a catalytic amount of bismuth(III) bromide in acetonitrile at room temperature. This selectivity was also achieved in the presence of terminal O,O-acetal functionality. The susceptibility of various other groups to cleavage was also investigated.

Synthesis of 4-azido-4-deoxy-Neu5,7,8,9Ac42en1Me. A key intermediate for the synthesis of GG167 from D-glucono-delta-lactone.

[reaction: see text] Stereoselective synthesis of 5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-4-azido-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enonic acid methyl ester, an advanced key intermediate for the synthesis of neuraminidase inhibitor GG167 (Zanamivir, Relenza), was accomplished using D-glucono-delta-lactone as starting material. A highly diastereoselective allyllation of an imine intermediate, a regioselective azide-opening of an aziridine, and chemoselective oxidations of vicinal diols served successfully as key steps.

Synthesis of a new stable conformationally constrained 2,7-anhydrosialic acid derivative.

A stereoseletive synthesis of 2,7-anhydrosialic acid derivative 18 was achieved from d-glucono-delta-lactone. A highly syn-selective addition of Grignard reagent to theN-benzylimine 8 served as a key step.

A new synthesis of Neu5Ac from D-glucono-delta-lactone.

A new route to Neu5Ac methyl ester (23) with a readily available sugar D-glucono-delta-lactone as starting material has been developed. A diastereoselective propargylation of alpha-acetamino aldehyde and a subsequent KMnO(4) oxidation of the terminal alkyne served as the key steps.