pH/redox/thermo-stimulative nanogels with enhanced thermosensitivity via incorporation of cationic and anionic components for anticancer drug delivery

To explore the potential biomedical applications of nanogels, it is a key factor to improve their thermosensitivity. In this paper, triple-responsive nanogels poly(N-isopropylacrylamide–N,N′-dimethylaminoethyl methacrylate–acrylic acid) (PNDA) were synthesized via in situ incorporating both cationic components and anionic components into a normal thermosensitive polymer matrix. The triple-monomer constructed PNDA nanogels displayed an enhanced thermosensitivity as compared with dual-monomer constructed PND nanogels. The PNDA nanogels presented higher encapsulation efficiency (～89%) and exhibited better pH/redox/thermo-responsivenesses in an anticancer drug delivery. In vitro biological study indicated that the PNDA nanogels have excellent biocompatibility and improved anticancer cytotoxicity to A549 cells after loading drug DOX.     

Synthesis,Structural Characterization,and Ability to Inhibit Cancer Growth of a Series of Organotin Poly(ethylene glycols)

A series of organotin poly(ethylene glycols) were synthesized including the first water soluble organotin polymers. These products are all polymeric with weight average molecular weights about 10⁵. Infrared spectroscopy shows the presence of moieties from both reactants and the formation of the Sn–O linkage. F MALDI MS shows the presence of up to over a hundred units and by isotopic abundance the presence of one, two, and three tin-containing ion fragments. The polymers inhibit the growth of cancer cell lines from bone, prostate, colon, breast, and lung cancers. In a number of instances chemotherapeutic index values of two and greater are found consistent with these polymers being more active against cancer cells than non-cancerous healthy cells. Thus, some of these polymers show good promise as a new family of anticancer drugs including the water-soluble organotin-containing polymers.     

Potential use of antioxidative mungbean protein hydrolysate as an anticancer asiatic acid carrier

This study investigated the potential use of mungbean (Vigna radiata (L.) Wilczek) protein hydrolysate (MPH) prepared from tryptic hydrolysis as an antioxidative hydrolysate and as a carrier for anticancer asiatic acid (AA). The antioxidant capacity of MPH was 0.67 and 0.46 ??mol Trolox equivalent (TE)/mg protein, as measured by oxygen radical absorbance capacity-fluorescein (ORAC_FL) and Trolox equivalent antioxidant capacity (TEAC) assays, respectively. Freeze-drying in lactose excipient reduced the antioxidant capacity of MPH to 0.48 ??mol TE/mg protein in ORAC_FL assay (P < 0.05) but did not alter antioxidant capacity determined by TEAC assay (P ≥ 0.05). The genotoxicity of H₂O₂ (50 ??M, 30 min) on hepatoblastoma HepG2 could be alleviated after HepG2 cells had taken up MPH after H₂O₂ exposure (P < 0.05). Moreover, the inhibition concentration (IC₅₀) of AA in HepG2 was lowered from 58.5 ??g mL^− 1 of AA alone to 38.5 ??g mL^− 1 when AA was freeze-dried with MPH in lactose excipient (P < 0.05). This study suggested that the efficacy of anticancer pentacyclic triterpene AA against hepatoblastoma HepG2 could be increased by co-drying with antioxidative mungbean protein hydrolysate in lactose excipient.     

Application of immobilized lipase in production of camptosar (CPT-11)

Lipase fromPseudomonas cepaica (Amano, PS-30) was immobilized on celite and used in organic solvent for the selective acylation of a key alcohol intermediate. The compound was transformed in the synthesis to the anticancer drug Camptosar (CPT-11). Catalyst activity was influenced by the water content and method used to dry the catalyst. This resolution has been conducted on production scale with equal weight of recyclable catalyst.     

Phenolic content, antioxidant, anti-inflammatory and anticancer activities of the edible halophyte Suaeda fruticosa Forssk

Suaeda fruticosa is an edible and medicinal halophyte known for its hypoglycaemic and hypolipidaemic activities. In this study, novel biological activities of the shoot extracts related to their phenolics were investigated. Results showed an appreciable total phenolic (31.8 mg GAE/g DW) in shoot extracts. The estimation of antioxidant capacities using oxygen radical absorbance capacity (ORAC method) and a cell based-assay (WS1) of four extracts (hexane, dichloromethane, methanol and water) showed that shoot methanol extract exhibit the highest antioxidant activities. The same extract displayed the utmost anti-inflammatory activity, inhibiting nitric oxide (NO) release, by 66.4% at 160 μg/ml in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Besides, the dichloromethane extract showed the highest anticancer activity against human lung carcinoma (A-549) and colon adenocarcinoma cell lines (DLD-1, Caco-2 and HT-29) with specificity against DLD-1 (IC₅₀ = 10 ± 1 μg/ml). These findings demonstrate the remarkable potentiality of this edible halophyte as valuable source of antioxidants which exhibit original and interesting anti-inflammatory and anticancer capacities.     

The selective delivery of anticancer agents using target-sensitive liposomes

Target-sensitive (TG-S) liposomes having modified antibodies on their surface were employed to study the release of calcein and the selective delivery of the anticancer agents, doxorubicin (DOX) and methotrexate (MTX). The release of calcein from TG-S liposome occurred when the various target cells were contacted with liposomes and it was proportionally increased with the increase of antibody affinity to the target cells. Increasing the concentration of antigen molecules (major histocompatibility, MHC) on the surface of RMA-S, the release of calcein and drugs from TG-S liposomes contacting with RMA-S also rised. The destabilization of TG-S liposomes was only induced above a threshold density of surface antigen on the target cell membrane. The growth inhibition of specific target cells by the liposomal drugs was always stronger than that of the non-specific ones. For specific target cells, the IC₅₀ of liposomal DOX was about 2 times greater than that of free DOX, on the while, for non-specific target cells, more than 5 times. This indicates that the liposomal drugs were transferred preferentially to the specific target cells than the non-specific ones. Based on this phenomenon, the TG-S liposomal MTX were also applied for the selective elimination of the specific target cells in the mixed culture of specific and non-specific target cells.     

抗癌药氟他胺的合成研究

以高纯度间三氟甲基苯胺为原料,经异丁酰氯酰化,再在助剂S存在下进行硝化制得氟他胺。本法大大降低邻硝基异构体的含量,产品收率≥67.5％。