Fabrication of poly(l-glutamic acid)/chitosan polyelectrolyte complex porous scaffolds for tissue engineering.

Porous scaffolds composed of polypeptides and polysaccharides have remarkable biocompatibility and potential to mimic an extracellular matrix for tissue engineering. This study presented a novel design of polyelectrolyte complex porous scaffolds of a synthetic polypeptide poly(l-glutamic acid) (PLGA) and a natural polysaccharide chitosan (CS) using a freeze drying method. The microstructure of the porous scaffolds could be adjusted by changing the freezing temperature and solid content of the reacting polymer.

Co-delivery of 10-hydroxycamptothecin with doxorubicin conjugated prodrugs for enhanced anticancer efficacy.

Well-defined amphiphilic linear-dendritic prodrugs (MPEG-b-PAMAM-DOX) are synthesized by conjugating doxorubicin (DOX), to MPEG-b-PAMAM through the acid-labile hydrazone bond. The amphiphilic prodrugs form self-assembled nanoparticles in deionized water and encapsulate the hydrophobic anticancer drug 10-hydroxycamptothecin (HCPT) with a high drug loading efficiency. Studies on drug release and cellular uptake of the co-delivery system reveal that both drugs are released in a pH-dependent manner and effectively taken up by MCF-7 cells.

Nanoscaled poly(L-glutamic acid)/doxorubicin-amphiphile complex as pH-responsive drug delivery system for effective treatment of nonsmall cell lung cancer.

Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Herein, we develop a polypeptide-based block ionomer complex formed by anionic methoxy poly(ethylene glycol)-b-poly(L-glutamic acid) (mPEG-b-PLG) and cationic anticancer drug doxorubicin hydrochloride (DOX·HCl) for NSCLC treatment. This complex spontaneously self-assembled into spherical nanoparticles (NPs) in aqueous solutions via electrostatic interaction and hydrophobic stack, with a high loading efficiency (almost 100%) and negative surface charge.

Facile one-pot synthesis of glucose-sensitive nanogel via thiol-ene click chemistry for self-regulated drug delivery.

A novel glucose-sensitive nanogel was conveniently prepared through one-pot thiol-ene copolymerization of pentaerythritol tetra(3-mercaptopropionate), poly(ethylene glycol) diacrylate, methoxyl poly(ethylene glycol) acrylate and N-acryloyl-3-aminophenylboronic acid. The formation of core-shell nanogel was verified by proton nuclear magnetic resonance, dynamic laser scattering (DLS) and transmission electron microscopy. The successful incorporation of phenylboronic acid (PBA) in the nanogel was confirmed through Fourier transform infrared spectroscopy, inductively coupled plasma mass spectrometry and fluorescence technology.

Nano-hydroxyapatite surfaces grafted with electroactive aniline tetramers for bone-tissue engineering.

An electroactive amino/carboxyl-capped aniline tetramer (AT) is covalently grafted to the surface of hydroxyapatite (HA) nanoparticles to generate novel electroactive HA-AT nanoparticles. The amount of AT ranges from 16.5 to 34.

Versatile biofunctionalization of polypeptide-based thermosensitive hydrogels via click chemistry.

In this study, we report thermosensitive hydrogels based on poly(ethylene glycol)-block-poly(γ-propargyl-l-glutamate) (PEG-PPLG). (13)C NMR spectra, DLS, and circular dichroism spectra were employed to study the mechanism of the sol-gel phase transition. Mouse fibroblast L929 cells were encapsulated and cultured within the hydrogel matrices, and the encapsulated cells were shown to be highly viable in the gel matrices, suggesting that the hydrogels have excellent cytocompatibilities.

A serum-tolerant hydroxyl-modified polyethylenimine as versatile carriers of pDNA/siRNA.

The polyethylenimine (PEI) derivatives (PTn) are prepared by treating PEI25k with Tris(hydroxymethyl) acrylamidomethane via the Michael addition. These PTns can effectively condense nucleic acids into nanosized particles with positive surface charges. The PTns show lower cytotoxicity and better serum-resistant capacity than PEI25k.

Biocompatible reduction-responsive polypeptide micelles as nanocarriers for enhanced chemotherapy efficacy in vitro.

To develop biocompatible reduction-responsive micellar systems for efficient intracellular drug delivery, disulfide-linked block copolymers of methoxyl poly(ethylene glycol) (mPEG) and poly(ε-benzyloxycarbonyl-l-lysine) (PZLL) were synthesized through ring-opening polymerization of ε-benzyloxycarbonyl-l-lysine N-carboxyanhydride with amino group terminated disulfide functionalized mPEG as macroinitiator. The copolymers self-assembled into micelles in phosphate buffered saline (PBS) at pH 7.4 through direct dissolution and dialysis methods.

Efficacious hepatoma-targeted nanomedicine self-assembled from galactopeptide and doxorubicin driven by two-stage physical interactions.

Polymers bearing pendant galactosyl group are attractive for targeted intracellular antitumor drug delivery to hepatoma cells (e.g. HepG2 and SMMC7721 cells) with asialoglycoprotein receptor (ASGP-R).

PEI conjugated gold nanoparticles: efficient gene carriers with visible fluorescence.

Low molecular weight polyethyleneimines were conjugated onto gold nanoparticles to form Au-PEI conjugates. Au-PEI is the first reported gene carrier which has both high transfection efficiency and strong fluorescence. Au-PEI showed higher transfection efficiency and it can be used for bioimaging because it can be detected by confocal laser scanning microscopy and in vivo bioimaging system.

Stimuli-sensitive synthetic polypeptide-based materials for drug and gene delivery.

Stimuli-sensitive synthetic polypeptides are unique biodegradable and biocompatible synthetic polymers with structures mimicking natural proteins. These polymers exhibit reversible secondary conformation transitions and/or hydrophilic-hydrophobic transitions in response to changes in environmental conditions such as pH and temperature. The stimuli-triggered conformation and/or phase transitions lead to unique self-assembly behaviors, making these materials interesting for controlled drug and gene delivery applications.

N-isopropylacrylamide-modified polyethylenimines as effective gene carriers.

25 kDa branched polyethylenimines are modified by N-isopropylacrylamide via Michael addition. An agarose gel retardation assay shows that all derivatives display good binding affinity toward plasmid DNA. The modified PEI-25K shows lower cytotoxicity in MTT assay and better transfection efficiency than unmodified PEI-25K in HeLa cells.

Methoxypoly(ethylene glycol)-block-poly(L-glutamic acid)-loaded cisplatin and a combination with iRGD for the treatment of non-small-cell lung cancers.

CDDP is loaded into methoxypoly(ethylene glycol)-block-poly(L-glutamic acid) (mPEG-b-PLG), and a combination with iRGD is applied for NSCLC chemotherapy. The CDDP-loaded micelles show sustained cisplatin release in PBS, dose- and time-dependent inhibition to HeLa and A549 cell proliferation, and no apparent hemolysis activities. In in vivo studies using subcutaneous NSCLC xenograft models (A549), both free CDDP and CDDP-loaded micelles show an evident anti-tumor effect.

Tunable pH-sensitive poly(β-amino ester)s synthesized from primary amines and diacrylates for intracellular drug delivery.

The pH sensitivity of a series of PbAEs synthesized from primary amines and diacrylates is studied. By changing alkyl groups of the amine monomers, the pKb can be tuned across a broad range (from 3.5 to 7.

Synthesis of biodegradable and electroactive tetraaniline grafted poly(ester amide) copolymers for bone tissue engineering.

Biodegradable poly(ester amide)s have recently been used as biomaterials due to their desirable chemical and biological characteristics as well as their mechanical properties, which are amendable for material processing. In this study, electroactive tetraaniline (TA) grafted poly(ester amide)s were successfully synthesized and characterized. The poly(ester amide)s-graft-tetraaniline copolymers (PEA-g-TA) exhibited good electroactivity, mechanical properties, and biodegradability.

Investigation of poly(lactide) stereocomplexes: 3-armed poly(L-lactide) blended with linear and 3-armed enantiomers.

Stereocomplex poly(lactide)s (sc-PLAs) were obtained from solution blending of 3-armed poly(L-lactide) (3PLLA) and linear poly(D-lactide) (PDLA) and between enantiomeric 3PLAs. Differential scanning calorimetry and wide-angle X-ray diffraction results indicated that racemic crystallites were preferentially produced in all the binary blends. The melting temperature and fusion enthalpy of racemic crystallites were remarkably different through varying the structure, constituent, and molecular weight of PLA.

Novel thermo- and pH-responsive hydroxypropyl cellulose- and poly (L-glutamic acid)-based microgels for oral insulin controlled release.

Novel smart microgel particles made of poly (L-glutamic acid-2-hydroxylethyl methacrylate) (PGH) and hydroxypropyl cellulose-acrylic acid (HPC-AA) have been successfully prepared via emulsion polymerization. The dynamic light scattering measurement reveals that the average hydrodynamic radius 〈Rh〉 and hydrodynamic radius distributions f (Rh) of the microgel particles depend on the temperature and pH value thus the microgel particles exhibit both pH- and temperature-sensitivity. In vitro release study shows that the amount of insulin released from microgels in the gastric juice (at pH 1.

An optical microscopy study on the phase structure of poly(L-lactide acid)/poly(propylene carbonate) blends.

The dependence of phase structure of PLLA/PPC blends on the blend ratio, the heat-treatment temperature and time was investigated by optical microscopy. It is found that, at lower PPC content, e.g.

Synthesis of isotactic-heterotactic stereoblock (hard-soft) poly(lactide) with tacticity control through immortal coordination polymerization.

A one-pot method for the preparation of a new family of PLA materials is reported that combines heterotactic (soft) and isotactic stereoblocks (hard). The ring-opening polymerization of rac-lactide with a salan-rare-earth-metal-alkyl complex in the presence of excess triethanolamine was performed in an immortal mode to give three-armed heterotactic poly(lactide) (soft) with excellent end-hydroxy fidelity. The in situ addition of a salen-aluminum-alkyl precursor to the above polymerization system under any monomer-conversion conditions activated the "dormant" hydroxy-ended PLA chains to propagate through the incorporation of the remaining rac-lactide monomer, but with isospecific selectivity (hard).

Decisive role of hydrophobic side groups of polypeptides in thermosensitive gelation.

Thermosensitive hydrogels based on PEG and poly(l-glutamate)s bearing different hydrophobic side groups were separately synthesized by the ring-opening polymerization (ROP) of l-glutamate N-carboxyanhydrides containing different alkyl protected groups, that is, methyl, ethyl, n-propyl, and n-butyl, using mPEG(45)-NH(2) as macroinitiator. The resulting copolymers underwent sol-gel transitions in response to temperature change. Interestingly, the polypeptides containing methyl and ethyl showed significantly lower critical gelation temperatures (CGTs) than those bearing n-propyl and butyl side groups.

Protic compound mediated living cross-chain-transfer polymerization of rac-lactide: synthesis of isotactic (crystalline)-heterotactic (amorphous) stereomultiblock polylactide.

A highly efficient strategy for one-pot synthesis of programmable, crystalline-amorphous stereomultiblock PLA from rac-lactide.

Hydrophobic poly (amino acid) modified PEI mediated delivery of rev-casp-3 for cancer therapy.

Recent studies in amphiphilic cationic polymers have demonstrated their potential as gene carriers with high transfection efficiency and low cytotoxicity in the in vitro settings to deliver drug, siRNA and plasmid DNA. Yet their safety and efficacy in vivo remain to be a challenge, and require further investigation. In our previous work, PP80 was synthesized as a novel amphiphilic cationic polymer by grafting hydrophobic polyphenylalanine segment on PEI, which displayed higher transfection efficiency than PEI in a number of cell lines in vitro.

Novel biodegradable and pH-sensitive poly(ester amide) microspheres for oral insulin delivery.

Biodegradable and pH-sensitive PEAs based on dual amino acids are designed, synthesized, and characterized. Insulin can be loaded into the PEA microspheres by a solid-in-oil-in-oil technique with high encapsulation efficiency. The feasibility of PEA microspheres as oral insulin delivery carriers is evaluated in vitro and in vivo.

Nanoporous multilayer poly(L-glutamic acid)/chitosan microcapsules for drug delivery.

Nanoporous poly(L-glutamic acid)/chitosan (PLGA/CS) multilayer microcapsules were fabricated by layer-by-layer (LbL) assembly using the porous silica particles as sacrificial templates. The LbL assembled nanoporous PLGA/CS microcapsules were characterized by Zeta-potential analyzer, FTIR, TGA, SEM, TEM and CLSM. 5-Fluorouracil (5-FU) was chosen as model drug.

Facile construction of functional biosurface via SI-ATRP and "click glycosylation".

Construction of high density glycosylated surfaces is important in the investigation of interactions between pathogens and surface carbohydrates. In this work, we provided a flexible method for glycosyl surface fabrication by combination of surface-initiated atom transfer radical polymerization (SI-ATRP) and copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction. Through this strategy, we got a very high surface glycosyl density of about 4 nmol/cm(2) with the surface "click" efficiency of nearly 50%.