Previous studies have reported that microRNAs regulate gene expression and transcription. miR-21 have been identified to play a role in many types of cancer. KLF5 functions as a tumor inhibitor in certain cancers. However, the role of KLF5 plays in hepatocellular carcinoma (HCC), especially concerning the relationship between miR-21 and the KLF5 gene remains to be determined. Reverse transcription-quantitative PCR (RT-qPCR), western blot analysis, as well as luciferase reporter and Transwell assays were used to determine the expression of miR-21 and KLF5 in Huh 7, SK-HEP-1, LO-2, and HCC tissues. In HCC cells and tissues, the upregulation of miR-21 was identified. HCC cell migratory and invasive abilities significantly increased because of miR-21 overexpression. KLF5 expression was inhibited by miR-21 by targeting its 3′-UTR. KLF5 overexpression alleviated the effect induced by miR-21 on the migratory and invasive ability of the Huh 7 cells. The results therefore show that, HCC cell migration and invasion is significantly suppressed by miR-21 via targeting KLF5. The newly identified miR-21/KLF5 axis provides a useful therapeutic biomarker for HCC treatment.

The development of novel thermo-, pH-and reduction-sensitive polymeric micelles based on a block copolymer p(PEG-MEMA-co-Boc-Cyst-MMAm-co-VI)-b-PEG (PPBV) for the intracellular delivery of anticancer drugs is reported. The pH/temperature-responsive behaviour of PPBV is observed by both DLS and UV-Vis experiments. The PPBV micelles prepared by a quick heating process are stable in PBS (pH 7.4, 37 C) for over 48 h and are stable in the presence of serum for at least 12 h. Paclitaxel (PTX) was loaded into the PPBV micelles with a high encapsulation efficiency (>85%), resulting in a high drug loading content (up to 26 wt%) by a simple heating method. The PTX-loaded micelles show slow drug release in PBS and rapid release after exposure to a weakly acidic pH or reductive environment. The PTX-loaded micelles showed higher cytotoxicity against HepG2 cells with increasing PTX concentration, whereas empty micelles are found to be non-toxic. These multi-sensitive polymeric micelles may serve as promising carriers for cytostatic drugs.

Novel pH and reduction dual‐sensitive biodegradable polymeric micelles for efficient intracellular delivery of anticancer drugs were prepared based on a block copolymer of methyloxy‐poly(ethylene glycol)‐b‐poly[(benzyl‐l‐aspartate)‐co‐(N‐(3‐aminopropyl) imidazole‐l‐aspartamide)] [mPEG‐SS‐P(BLA‐co‐APILA), MPBA] synthesized by a combination of ring‐opening polymerization and side‐chain reaction. The pH/reduction‐responsive behavior of MPBA was observed by both dynamic light scattering and UV–vis experiments. The polymeric micelles and DOX‐loaded micelles could be prepared simply by adjusting the pH of the polymer solution without the use of any organic solvents. The drug release study indicated that the DOX‐loaded micelles showed retarded drug release in phosphate‐buffered saline at pH 7.4 and a rapid release after exposure to weakly acidic or reductive environment. The empty micelles were nontoxic and the DOX‐loaded micelles displayed obvious anticancer activity similar to free DOX against HeLa cells. Confocal microscopy observation demonstrated that the DOX‐loaded MPBA micelles can be quickly internalized into the cells, and effectively deliver the drugs into nuclei. Thus, the pH and reduction dual‐responsive MPBA polymeric micelles are an attractive platform to achieve the fast intracellular release of anticancer drugs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1771–1780

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Peptide self-assembling materials have recently emerged as one of the most promising biomaterials. In this study, we synthesized three amphipathic cyclopeptides (CPs1-3) with systematically modified side chains to control the morphologies of self-assembly. Owing to the varying modifications of the side chains, various micro/nanostructures were achieved because of different driving forces. The obtained morphologies were characterized by transmission electron microscopy (TEM) and scanning electron microscope (SEM). Apart from hydrogen bond interactions for CPs, CP1 self-assembles into spindlelike aggregates with an average diameter of 70 nm and a length of 300 nm owing to the salt-bridge interactions in a neutral medium. CP2 can form micro/nanotubes with the diameters ranging from 750 nm to 2 mm via the hydrophilic and hydrophobic interactions between the cyclopeptide ring and the alkyl chain. While CP3 forms solid nanospheres with an average diameter of 516 nm through aromaticaromatic p-p interactions. This approach can lead to the fabrication of new functional supramolecular assemblies and materials and broaden the insights for the mechanism of the self-assembly.

Biodegradable amphiphilic ABC Y-shaped triblock copolymer (MPBC) containing PEG, PBLA, and PCL segments was synthesized via the combination of enzymatic ringopening polymerization (ROP) of epsilon-caprolactone, ROP of BLA-N-carboxyanhydride and click chemistry, where PEG, PBLA, and PCL are poly(ethylene glycol), poly(benzyl-L-aspartate), and polycaprolactone, respectively. Propynylamine was employed as ROP initiator for the preparation of alkynylterminated PBLA and methyloxy-PEG with hydroxyl and azide groups at the chain-end was used as enzymatic ROP initiator for synthesis of monoazido-midfunctionalized block copolymer mPEG-b-PCL. The subsequent click reaction led to the formation of Y-shaped asymmetric heteroarm terpolymer MPBC. The polymer structures were characterized by different analyses. The MPBC terpolymer self-assembled into micelles and physically encapsulated drug doxorubicin (DOX) to form DOXloaded micelles, which showed good stability and slow drug release. In vitro cytotoxicity study indicated that the MPBC micelles were nontoxic and the DOX-loaded micelles displayed obvious anticancer activity similar to free DOX against HeLa cells.

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. Because the surface-bound vicinal diol structural motifs have an ability to form hydrogen bonds with the peptide segments on the nanofibers, which restrain and disturb the hydrogen-bonding interaction among the nanofibers, the network structure formed based on the entanglement of nanofibers via hydrogen-bonding interaction is destroyed, which leads to a gel-sol transition. The novel concept of post-self-assembly modification demonstrated here could lead to a new technique for using self-assembled nanostructures in the emerging fields of nanoscience and nanotechnology.

The pH-sensitive tertiary amino groups were introduced to synthesize temperature and pH dual-sensitive degradable polyaspartamide derivatives (phe/DEAE-g-PHPA) containing pendant aromatic structures and ionizable tertiary amino groups. The thermo/pH-responsive behavior of phe/ DEAE-g-PHPA polymer can be tuned by adjusting the graft copolymer composition. Due to the pH sensitivity of the phe/ DEAE-g-PHPA-g-mPEG polymer with hydrophilic long PEG chain, the micelles and the anticancer drug-loaded micelles were prepared by a quick pH-changing method without using toxic organic solvent. The obtained polymeric micelles, paclitaxel-loaded micelles and doxorubicin-loaded micelles were stable under physiological conditions. Both the drugloaded micelles showed much faster release at pH 5 than at pH 7.4. The doxorubicin-loaded micelles showed obvious and better anticancer activity against both HepG2 and HeLa cells than free doxorubicin. Thus these nontoxic, dual thermo-and pHsensitive phe/DEAE-g-PHPA-g-mPEG micelles may be a promising anticancer drug delivery system.