A single-monomer derived linear-like PEI-co-PEG for siRNA delivery and silencing.

Polyethylenimines (PEIs) are commonly used as a vehicle to deliver and protect siRNA, but the strong interaction still remains to be modulated for efficient siRNA release and silencing. Herein, a single-monomer derived linear-like PEI-co-PEG (LPEI-co-PEG, P(2)) was synthesized to substantially enhance the siRNA release, but not affect the efficiency of protection. The linear-like copolymer (P(2)) was only synthesized from a single-monomer by intensive synchrotron X-ray irradiation within 5 min, randomly producing both PEI and PEG segments. The counterpart vehicle, LPEI (P(1)), was also synthesized for comparison. We found that the P(1) and P(2) were able to prevent siRNA against enzymatic degradation. Most importantly, efficient siRNA release (52%) was only observed in the siRNA/P(2) complexes and not in the siRNA/P(1) complexes (<5%), suggesting that the PEG segment may modulate the interaction between siRNA and P(2) segment. Specifically, P(2) as well as P(1) can emit photoluminescence; cancer cells exhibited a detectable photoluminescence after treatment with P(1) and P(2), indicative of their excellent transfection efficiency. Subsequently, the siGFP/P(2) complexes knocked down GFP with excellent efficiency (75%) above the siGFP/P(1) complexes (19%) and siGFP/Lipofectamine complexes (20%). Importantly, the siRNA with anti-VEGF function being associated with P(2) have been demonstrated an excellent efficiency in the suppression of tumor growth.

One-pot synthesis of linear-like and photoluminescent polyethylenimines for intracellular imaging and siRNA delivery.

Linear-like and photoluminescent polyethylenimines (LPEIs) were synthesized through a one-pot reaction within 5 min using synchrotron radiation for intracellular imaging and siRNA delivery.

Enhanced quantum yield of dendrimer-entrapped gold nanodots by a specific ion-pair association and microwave irradiation for bioimaging.

A specific ion-pair approach can be involved in precise control of the size of gold nanodots. The dendrimers with terminal amine and hydroxyl groups were a hydrophilic and hydrophobic microcavity-template, respectively, for trapping gold salts. The facile strategy can significantly enhance the quantum yield of gold nanodots from 20% to 62% after microwave irradiation.

Effects of peptidic antagonists of Grb2-SH2 on human breast cancer cells.

The growth factor receptor-bound protein Src homology 2 (Grb2-SH2) plays an important role in the oncogenic Ras signaling pathway, which involves in cell proliferation and differentiation. Therefore, the antagonist of Grb2-SH2 has become a potential target for developing anticancer agents. Recently, we discovered a peptide 1 (Fmoc-Glu-Tyr-Aib-Asn-NH(2)) with high affinity for the Grb2-SH2 domain by using surface plasmon resonance (SPR)-biosensor technology. Herein, we report the further design of the lead peptide 1 by addition of an Arg-Gly-Asp sequence to 1 to enhance binding to Grb2-SH2 and inducing apoptosis in cancer cells. Both the linear and cyclic analogs of the newly designed compound were prepared along with an analog in which the N(alpha)-Fmoc group was removed. These peptide analogs were assayed for their affinity for the Grb2-SH2, their antiproliferative effect on human breast cancer cells, their specificity for cancer cells, and their effects on cytotoxicity and the cell cycle. MCF-7 and MDA-MB-453 breast cancer cells were treated with various concentrations of each peptide. The cell viability and cytotoxicity of peptide-treated cells were determined by using the cell proliferation kit (3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-tetrazolium bromide, MTT) and cytotoxicity kit (lactate dehydrogenase, LDH), respectively. Effects of peptides on the cell cycle progression of cancer cells and apoptosis were analyzed by using flow cytometry. Results demonstrated that the peptide analog 2 (H-Arg-Gly-Asp-Glu-Tyr-Aib-Asn-Arg-Gly-Asp-NH(2)) had anti-proliferative effects on MCF-7 and MDA-MB-453 cells with an IC(50) of 45.7 microM and 47.4 microM, respectively. The cytotoxicity and percentage of sub-G1 in the cell cycle were increased in these cancer cells when cells were treated with higher concentration of the Arg-Gly-Asp-containing peptide 2. These results provide important information for the development of anti-cancer agents.