Development of novel cell-penetrating peptide Cys-CPT2,9 penetratin with high translocation ability and antitumor activity / 药学学报

To develop a cell-penetrating peptide with high membrane penetrating ability and effective antitumor activity, we designed and synthesized an analogue of penetratin, [Cys-CPT2,9] penetratin, by substitution of Gln2 and Asn9 with Cys-CPT. We investigated the transmembrane activity and antitumor activity of [Cys-CPT2,9] penetratin. The fluorescence intensity of [Cys-CPT2,9] penetratin in HeLa cells was observed by laser confocal microscopy and flow cytometry, and the cell uptake mechanism of [Cys-CPT2,9] penetratin was evaluated by using different endocytic inhibitors, finally the anti-tumor activity of [Cys-CPT2,9] penetratin was tested by MTT assay. The results showed that the membrane activity of [Cys-CPT2,9] penetratin was significantly enhanced in laser confocal microscopy and flow cytometry assay, and the intracellular fluorescence intensity was 5 times higher than penetratin. The cell uptake mechanism study of [Cys-CPT2,9] penetratin indicated that it mainly entered the cell through the clathrin and endocytosis. Moreover, [Cys-CPT2,9] penetratin exhibited anti-tumor activity against HeLa cells, and its inhibitory effect on cancer cells was stronger than CPT. [Cys-CPT2,9] penetratin is a new cell-penetrating peptide with high translocation ability, and has anti-tumor activity against HeLa cells.

In vivo and in vitro anti-inflammatory effects of ethanol fraction from Periploca forrestii Schltr / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the anti-inflflammatory effects of an ethanol fraction of Periploca forrestii Schltr. (EFPF) and to investigate the potential mechanisms underlying in vivo and in vitro models.</p><p><b>METHODS</b>The antiinflflammatory effects of EFPF were evaluated using the xylene-induced mouse ear edema and carrageenan-induced rat paw edema models in vivo. In vitro, RAW264.7 cells were exposed to 0-800 μg/mL EFPF and the cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Then cells were treated with different concentrations of EFPF (100-400 μg/mL) and stimulated with lipopolysaccharide (LPS, 1 μg/mL) for 24 h. The supernatant was analyzed for nitric oxide (NO) using the Griess reagent, and the levels of inflflammatory mediators and cytokines were determined using enzyme-linked immunosorbent assays for prostaglandin E(PGE), tumor necrosis factor α (TNF-α), interleukin (IL) 6, and IL-10. The protein expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor κB (NF-κB), and mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK were examined by Western blot.</p><p><b>RESULTS</b>Compared with the control group, EFPF signifificantly reduced mouse ear edema and rat paw edema rate (P<0.05 or P<0.01). Compared with the LPS group, EFPF signifificantly inhibited the LPS-stimulated production of NO, PGE, TNF-α and IL-6 (P<0.05 or P<0.01), and increased the IL-10 production (P<0.05). EFPF also signifificantly inhibited LPS-induced protein expressions of iNOS and COX-2, suppressed the phosphorylation and degradation of inhibitor of NF-κB-α, decreased p65 level, and inhibited the phosphorylation of p38, ERK1/2 and JNK P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>EFPF exerted anti-inflflammatory effect by reducing protein expressions of iNOS and COX-2 and the production of the inflflammation factors, including TNF-α, IL-6, NO and PGE, mainly through inhibition of LPS-mediated stimulation of NF-κB and MAPK signaling pathways.</p>

Advances of tumor targeting peptides drug delivery system with pH-sensitive activities / 药学学报

The pH-sensitive peptides drug delivery systems, which target to acidic extracellular environment of tumor tissue, have many advantages in drug delivery. They exhibit a high specificity to tumor and low cytotoxicity, which significantly increase the efficacy of traditional anti-cancer drugs. In recent years the systems have received a great attention. The pH-sensitive peptides drug delivery systems can be divided into five types according to the difference in pH-responsive mechanism, type of peptides and carrier materials. This paper summarizes the recent progresses in the field with a focus on the five types of pH-sensitive peptides in drug delivery systems. This may provide a guideline to design and application of tumor targeting drugs.

Carboxyl nanodiamond as intracellular transporters of anticancer drug--podophyllotoxin / 药学学报

The purpose of this study is to investigate the intracellular transporters effect and the cytotoxicity of carboxyl nanodiamond (CND) - podophyllotoxin (PPT). Nanodiamond (ND) was treated with mixed carboxylic acid and finally got 64 nm CND by centrifugation, and then it was reacted with PPT to form CND-PPT. UV spectrophotometry was used to calculate the content of PPT in CND-PPT, the particle size distribution and zeta potential were measured by Dynamic laser scattering instrument. CND, PPT, CND-PPT and CND + PPT (physical mixture of CND and PPT) were characterized by Fourier transform infrared spectroscopy, at the same time, thermal analysis and element analysis were used to estimate the content of the PPT in CND-PPT. The affect of CND, PPT, CND-PPT on HeLa cell was measured with MTT assay. The results showed that content of PPT combined with CND accounted for about 10%. MTT assay showed that CND has low cytotoxicity and CND-PPT can increase the water soluble of PPT. As a conclusion, CND as a hydrophilic pharmaceutical carrier combined with PPT is able to increase the water solubility of PPT, at low concentration, CND-PPT can enhance the antitumor activity in comparison with PPT, so CND can be used as a potential anticancer drug carrier.

Advances in parallel artificial membrane permeability assay and its applications / 药学学报

With the development of drug discovery, more and more candidate compounds need to be studied. Methods that can screen compound rapidly received significant attention. Parallel artificial membrane permeability assay (PAMPA) as a powerful tool has been applied to drug studies. It uses an artificial lipid membrane to mimic the barrier for drug permeability studies. This article introduces the establishment and characteristics of PAMPA, as well as its applications in screening compounds. It can be used as models (e.g. predicting the ability of compound in gastro-intestinal absorption, blood-brain barrier transportation and skin penetration) by changing the component of artificial lipid membrane. PAMPA has advantages in high throughput selection of valuable compound with low cost, versatile, low dose, and good reproducibility.

Studies on antitumor effects of podophyllotoxin nanoliposome / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the antitumor effects of the podophyllotoxin nanoliposome and the suspensions of podophyllotoxin in bearing-tumor mice.</p><p><b>METHOD</b>The experimental mice were inoculated by suspension liquid of tumor cell in axillary region near the forelimb, 0.2 mL each. The mice had been randomly divided into 8 groups 24 h latter. The podophyllotoxin nanoliposome, suspension liquid of the podophyllotoxin, CX or NS was given to each group respectively. Except CX was given by celiac injection once, the other groups were injected every 4 days for three times. The mice were killed by hauling necks on the twelfth day after treatment, the tumor was weighed and the inhibitory rate was calculated.</p><p><b>RESULT</b>When the dosage of podophyllotoxin nanoliposome and the suspensions of podophyllotoxin reached 5.0 mg x kg(-1), the rate of inhibiting tumor were 52.37% and 38.25% to the H22 liver cancer of mice respectively.</p><p><b>CONCLUSION</b>Podophyllotoxin nanoliposome and the suspensions of podophyllotoxin have the effect in anti-liver cancer. And podophyllotoxin nanoliposome have stronger inhibitory rate compared with suspension liquid of the podophyllotoxin in same dose.</p>