Multibarrier-penetrating drug delivery systems for deep tumor therapy based on synergistic penetration strategy.

Nanotherapies, valued for their high efficacy and low toxicity, frequently serve as antitumor treatments, but do not readily penetrate deep into tumor tissues and cells. Here we developed an improved tumor-penetrating peptide (TPP)-based drug delivery system. Briefly, the established TPP iNGR was modified to generate a linear NGR peptide capable of transporting nanotherapeutic drugs into tumors through a CendR pathway-dependent, neuropilin-1 receptor-mediated process. Although TPPs have been reported to reach intended tumor targets, they often fail to penetrate cell membranes to deliver tumoricidal drugs to intracellular targets. We addressed this issue by harnessing cell penetrating peptide technology to develop a liposome-based multibarrier-penetrating delivery system (mbPDS) with improved synergistic drug penetration into deep tumor tissues and cells. The system incorporated doxorubicin-loaded liposomes coated with nona-arginine (R9) CPP and cyclic iNGR (CRNGRGPDC) molecules, yielding Lip-mbPDS. Lip-mbPDS tumor-targeting, tumor cell/tissue-penetrating and antitumor capabilities were assessed using CD13-positive human fibrosarcoma-derived cell (HT1080)-based in vitro and in vivo tumor models. Lip-mbPDS evaluation included three-dimensional layer-by-layer confocal laser scanning microscopy, cell internalization/toxicity assays, three-dimensional tumor spheroid-based penetration assays and antitumor efficacy assays conducted in an animal model. Lip-mbPDS provided enhanced synergistic drug penetration of multiple biointerfaces for potentially deep tumor therapeutic outcomes.

Fruit sphere microenvironments and berry phenolic content of Cabernet Sauvignon (Vitis vinifera L.) cultivated under rain-shelter systems with coloured plastic film

Abstract Rain-shelter cultivation has been proven an important cultivation method for grape-plantings in continental monsoon climate zones, of which white plastic films are the most common shelter material. However, while this method and material reduces the occurrence of the disease, it can also decrease the grape berry quality. Five colours (including red, yellow, blue, purple, and white) of plastic films were covered above Cabernet Sauvignon (Vitis vinifera L.) grapevine rows before veraison. Rain-shelter cultivation reduced air temperature, wind speed, and total solar radiation and enhanced relative humidity in the fruit sphere of grapevines. For each particular colour plastic film, the irradiance of its corresponding spectrum band in the canopy of vines was higher than with other colour plastic films. Meanwhile, the blue plastic film treatment significantly promoted the accumulation of total phenolics, anthocyanins, flavonoids, tannins, and phenolic acids more than the other colours of plastic films. Blue plastic films are more beneficial for berry quality promotion of wine grapes, especially Cabernet Sauvignon, under rain-shelter cultivation in continental monsoon climate zones.

Protective effect of anthocyanins from lingonberry on radiation-induced damages.

There is a growing concern about the serious harm of radioactive materials, which are widely used in energy production, scientific research, medicine, industry and other areas. In recent years, owing to the great side effects of anti-radiation drugs, research on the radiation protectants has gradually expanded from the previous chemicals to the use of natural anti-radiation drugs and functional foods. Some reports have confirmed that anthocyanins are good antioxidants, which can effectively eliminate free radicals, but studies on the immunoregulatory and anti-radiation effects of anthocyanins from lingonberry (ALB) are less reported. In this experiment, mice were given orally once daily for 14 consecutive days before exposure to 6 Gy of gamma-radiation and were sacrificed on the 7th day post-irradiation. The results showed that the selected dose of extract did not lead to acute toxicity in mice; while groups given anthocyanins orally were significantly better than radiation control group according to blood analysis; pretreatment of anthocyanins significantly (p < 0.05) enhanced the thymus and spleen indices and spleen cell survival compared to the irradiation control group. Pretreatment with anthocyanins before irradiation significantly reduced the numbers of micronuclei (MN) in bone marrow polychromatic erythrocytes (PCEs). These findings indicate that anthocyanins have immunostimulatory potential against immunosuppression induced by the radiation.

Evaluation of antioxidant and antiproliferative properties of three Actinidia (Actinidia kolomikta, Actinidia arguta, Actinidia chinensis) extracts in vitro.

The total phenolic content, total flavonoid content, vitamin C content, and antioxidant activities of ethanol extracts from different kiwifruit varieties (Actinidia kolomikta, Actinidia arguta, Actinidia chinensis) were determined in this study. Multiple scavenging activity assays including the hydroxyl radical, O(2) (-)·radical, DPPH, and the ABTS(+) radical scavenging activity assays were used to identify the antioxidant activities of Actinidia extracts. The cell viability of HepG2 and HT-29 cells was also examined in this study. The results demonstrated that the Actinidia kolomikta extract had a higher antioxidant activity than the other two Actinidia extracts. There is a positive correlation between antioxidant activity and the polyphenols and vitamin C content in all three extracts (R(2) ≥ 0.712, p < 0.05). The Actinidia arguta extract had the highest inhibitory effect on HepG2 and HT-29 cell growth. These results provide new insight into the health functions of fruit and demonstrate that Actinidia extracts can potentially have health benefits.