Fabrication of tough poly(ethylene glycol)/collagen double network hydrogels for tissue engineering.

In this study, a series of poly(ethylene glycol)/collagen (PEG/Col) double network (DN) hydrogel is fabricated from PEG and Col. Results of the compressive strength test indicate that the strength and toughness of these DN hydrogels are significantly enhanced. The fracture strength of PEG/Col DN hydrogels increases by 9- to 12-fold compared with that of PEG single network (SN) hydrogel, and by 36- to 48-fold compared with that of Col SN hydrogel.

[Endocytosis pathway and intracellular distribution of heparosan].

In this study, the endocytosis pathway of heparosan and its intracellular distribution were investigated in MCF-7 tumor cells and COS7 normal cells. The endocytosis inhibition and cellular probe location experiments showed that MCF-7 tumor cells took heparosan more efficiently and selectively than COS7 cells. The cellular uptake of heparosan was energy-dependent in both MCF-7 tumor cells and COS7 normal cells.

In situ supramolecular hydrogel based on hyaluronic acid and dextran derivatives as cell scaffold.

In this study, hyaluronic acid-β-cyclodextrin conjugate (HA-CD) and dextran-2-naphthylacetic acid conjugate (Dex-NAA) were synthesized as two gelators. The degrees of substitution (DS) of these two gelators were determined to be 15.5 and 7.

One-pot construction of boronate ester based pH-responsive micelle for combined cancer therapy.

In this study, one-pot strategy for the construction of micelles loaded with two types of anticancer drugs (i.e., doxorubicin and methotrexate) together is reported.

Hyaluronic acid and polyethylenimine self-assembled polyion complexes as pH-sensitive drug carrier for cancer therapy.

In this study, a series of polyion complexes (PICs) were prepared via electrostatic interaction between hyaluronic acid-histidine conjugate (HH) and polyethylenimine-histidine conjugate (PH). These PICs with the average size ranging from 410.5 nm to 98.

Heparosan based negatively charged nanocarrier for rapid intracellular drug delivery.

In this study, a heparosan-DOX conjugate (HDC) was designed and prepared by covalently linking heparosan with anticancer drug doxorubicin (DOX) via "Schiff" base. Due to the amphiphilic nature, the HDC could self-assemble into nanoparticles in aqueous solution of pH 7.4.

Fabrication of doxorubicin and heparin co-loaded microcapsules for synergistic cancer therapy.

In this study, a layer-by-layer (LbL) assembly (HEP/CHI)5 microcapsule with doxorubicin hydrochloride (DOX) encapsulating inside was fabricated via alternatively depositing heparin (HEP) and chitosan (CHI) onto DOX-loaded CaCO3 templates. The microcapsules were of stable architecture and had good dispersity in aqueous medium. Fluorescence observation showed that DOX distributed both in the wall and in the cavity of microcapsules, while HEP presented in the capsule wall.

Construction of serum resistant micelles based on heparosan for targeted cancer therapy.

A novel micelle based on heparosan and deoxycholic acid (DOCA) conjugate (HD) as drug carrier was reported here. As the surface was negatively charged, this micelle could resist serum adsorption, showing favorable stability. Moreover, fluorescence observation confirmed that it was able to deliver model hydrophobic drug doxorubicin (DOX) into HeLa cells efficiently.

Multi-functional envelope-type nanoparticles assembled from amphiphilic peptidic prodrug with improved anti-tumor activity.

A novel multifunctional amphiphilic peptidic prodrug was reported here by conjugating the antitumor drug of doxorubicin (DOX) to the hydrophobic tail of a designed peptide-amphiphile (PA), in which the hydrophilic peptide headgroup comprises a glycine-arginine-glycine-aspartic acid-serine (GRGDS) sequence and octaarginine (R8) sequence. Because of the amphiphilic nature, this peptidic prodrug can spontaneously self-assemble into spherical multifunctional envelop-type nanoparticles (MENPs) with the functional peptide sequences gathered on surface. By means of the multifunctions of RGD-mediated tumor targeting, R8-mediated membrane penetration and intracellular protease-mediated hydrolyzing peptide bonds, the MENPs could targeted deliver doxorubicin (DOX) to tumor cells, showing improved antitumor activity both in vitro and in vivo with much reduced side effects.

A new anti-cancer strategy of damaging mitochondria by pro-apoptotic peptide functionalized gold nanoparticles.

Gold nanoparticles functionalized with pro-apoptotic peptide (PAP-AuNPs) were fabricated, which were able to lead to programmed cell-death by damaging mitochondria.

Self-assembled BolA-like amphiphilic peptides as viral-mimetic gene vectors for cancer cell targeted gene delivery.

In this study, two types of BolA-like amphiphilic peptides with dual ligands comprising a tumor-targeting moiety of RGD sequence and a cell-penetrating moiety of R8 sequence are designed and synthesized as gene vectors. The BolA-structural peptide carriers can self-assemble into spherical nanoparticles with a hydrophilic core and shell, which are similar to the viral capsid and can bind plasmid DNA in an aqueous medium to form viral-mimetic complexes. It is found that the BolA-like dual ligands system exhibits significantly enhanced gene expression in both HeLa and 293T cell lines, as compared with poly(ethylenimine) PEI.

Novel gene transfer vectors based on artificial recombinant multi-functional oligopeptides.

Viral vectors, except for their safety concern, have shown high efficiency in both delivery and expression of gene. Here, a series of new gene carriers, comprised of short peptide subunits with special functions to imitate viral vectors, were designed and three vectors, (C(18))(2)KH(4)R(8)GDS, AcKH(4)R(8)GDS and (C(18))(2)KH(4)R(8), designated as ARM1, ARM2, ARM3, respectively, were synthesized and evaluated. The transfection efficiency in vitro was studied in terms of 293T, HepG2 and HeLa cell lines.

Facile construction of nanofibers as a functional template for surface boron coordination reaction.

A facile strategy to perform the boron coordination reaction on a template of nanofibers is developed. Peptides with phenylboronic acid tails (peptidyl boronic acids) are designed and prepared as building blocks that can self-assemble into nanofibers. After the addition of vicinal diol structural motifs to the self-assembling system, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry indicates that the boron coordination reaction occurs on the template of nanofibers, which results in the increase of the width and roughness of the nanofibers as demonstrated by transmission electron microscopy and atomic force microscopy measurements.

Surface self-assembly of N-fluorenyl-9-methoxycarbonyl diphenylalanine on silica wafer.

N-Fluorenyl-9-methoxycarbonyl diphenylalanine (Fmoc-FF-OH) was chemically immobilized to the surface of silica wafer as the "seed". When immersing this peptide attached silica wafer into the dipeptide aqueous solution, the occurrence of a pH triggered surface self-assembly resulted in the formation of peptide nanorods on the surface of silica wafer. This surface self-assembly exhibited a dependence on the concentration of the dipeptide aqueous solution.

Supramolecular architectures self-assembled from asymmetrical hetero cyclopeptides.

In this study, two asymmetrical cyclopeptides (CP1 and CP2) were designed and synthesized. The self-assembly behaviors of the asymmetrical cyclopeptides at varying pHs were investigated in terms of transmission electron microscopy (TEM), circular dichroism (CD), and Fourier transform infrared (FT-IR) spectroscopy. It was found that the self-assembly of CP1 resulted in the formation of nanofibers with α-helix conformation, while CP2 self-assembled into well-ordered nanorods with anti-parallel β-sheet conformation.

Construction of cell penetrating peptide vectors with N-terminal stearylated nuclear localization signal for targeted delivery of DNA into the cell nuclei.

Cellular uptake and nuclear localization are two barriers to gene delivery. Here, we designed new gene delivery carriers with an N-terminal stearylated (STR) nuclear localization signal (NLS), PKKKRKV, present in the Simian Virus 40 large T antigen with the aim to overcome limitations, such as cell membrane and nuclear pores, offering attractive possibilities to enhance gene delivery. Four vectors with different structures of N-stearylated nuclear localization signal-octaarginine peptide (STR-PKKKRKV-R(8) or STR-NLS-R(8), STR-VKRKKKP-R(8) or STR-reverse NLS-R(8), PKKKRKV-R(8) or NLS-R(8), and VKRKKKP-R(8) or reverse NLS-R(8)) were compared.

Construction of surfactant-like tetra-tail amphiphilic peptide with RGD ligand for encapsulation of porphyrin for photodynamic therapy.

A surfactant-like tetra-tail amphiphilic peptide, [(C(18))(2)K](2)KR(8)GRGDS was designed and synthesized for targeted drug delivery. The resulting peptide-amphiphile, consisting of four hydrophobic aliphatic tails and a hydrophilic peptide head group, was able to self-assemble into nanosized micelles in aqueous medium at low concentration. Ibuprofen and doxorubicin (DOX) was loaded into peptide micelles as model hydrophobic drugs respectively, and the sustained release behavior was observed.

Core-shell nanosized assemblies mediated by the alpha-beta cyclodextrin dimer with a tumor-triggered targeting property.

In this paper, the alpha-beta cyclodextrin dimer is designed via "click" chemistry to connect the hydrophilic and hydrophobic segments to form self-assembled noncovalently connected micelles (NCCMs) through host-guest interactions. A peptide containing the Arg-Gly-Asp (RGD) sequence was introduced to NCCMs as a target ligand to improve the cell uptake efficacy, while PEGylated technology was employed via benzoic-imine bonds to protect the ligands in normal tissues and body fluid. In addition, two fluorescent dyes were conjugated to different segments to track the formation of the micelles as well as the assemblies.

Amphiphilic cationic lipopeptides with RGD sequences as gene vectors.

Two kinds of arginine-rich amphiphilic lipopeptides with hydrophobic aliphatic tails (C(12)GR(8)GDS, LP1 and C(18)GR(8)GDS, LP2) were designed and synthesized as functional gene vectors. With hydrophobic tail modification, these amphiphilic lipopeptides could bind DNA more efficiently and form stable spherical complexes in comparison with the control peptide (AcGR(8)GDS, P1). Moreover, the size and zeta potential results demonstrated the charge density and stability of the vector/DNA complexes could be improved with the increasing length of the aliphatic tails.