Amonafide, a naphthalimide derivative, although selected for exploratory clinical trials for its potent anticancer activity, has long been challenged by its unpredictable side effects. In the present study, a novel amonafide analogue, 2-(2-dimethylamino)-6-thia-2-aza-benzo-[def]-chrysene-1,3-diones (R16) was synthesized by substituting 5 ¶-NH 2 of the naphthyl with a heterocyclic group to amonafide, with additional introduction of a thiol group. In a panel of various human tumor cell lines, R16 was more cytotoxic than its parent compound amonafide. It was also effective against multidrug-resistant cells. Importantly, the i.p. administration of R16 inhibited tumor growth in mice implanted with S-180 sarcoma and H 22 hepatoma. The molecular and cellular machinery studies showed that the R16 functions as a topoisomerase II (topo II) poison via binding to the ATPase domain of human topo IIA. The superior cytotoxicity of R16 to amonafide was ascribed to its potent effects on trapping topo II -DNA cleavage complexes. Moreover, using a topo II catalytic inhibitor aclarubicin, ataxia-telangiectasia-mutated (ATM)/ATMand Rad3-related (ATR) kinase inhibitor caffeine and topo II -deficient HL-60/MX2 cells, we further showed that R16-triggered DNA double-strand breaks, tumor cell cycle arrest, and apoptosis were in a topo II -dependent manner. Taken together, R16 stood out by its improved anticancer activity, appreciable anti -multidrug resistance activities, and well-defined topo II poisoning mechanisms, as comparable with the parent compound amonafide. All these collectively promise the potential value of R16 as an anticancer drug candidate, which deserves further development. [Mol Cancer Ther 2007;6(2):484 -95]

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An efficient and green preparation strategy is critical in promoting the marketization of expanded polypropylene (EPP) products. In this work, supercritical CO2 extrusion foaming in cooperating with wind-cooling granulator technology was creatively used to prepare polypropylene (PP)/thermoplastic polyurethane (TPU) composite bead foams with controllable cellular structures and geometric shapes like capsule, sphericity, and pie shaped. It is found that the addition of TPU can help to promote uniform cellular structures. More importantly, the procedure of polymer melting, gas dispersion, foaming, and pelletizing can be completed in a one-step continuous process, with the advantages of high efficiency, low cost, controllable microstructures of the bead foams, and so on. Besides, the effect of processing parameters on the cellular structures, expansion ratio, and open-cell content of the bead foams was studied. Specifically, the cell growth progress and morphology evolution of the composite foam beads were recorded by a high-definition camera and microtechniques. In addition, the extruded bead foams were shaped into the foam board via steam-chest molding, and its interbead bonding mechanism and thermal insulation properties were studied. The as-prepared foam board exhibits low density (0.08 g/cm3) and thermal conductivity (46 mW/(m K)), which are expected to be used in the field of thermal insulation. This project contributes to the establishment of large-scale preparation and theory of bead foams and is expected to be applied to other polymeric foams.

Foam injection molding (FIM) is an advanced technology for preparing lightweight plastic foams, but its inferior mechanical performance remains a challenge. In this study, microcellular injection-molded β-polypropylene (β-PP) foams with high ductility were successfully prepared by combing the β-nucleating agent with controllable temperature field. Foaming results showed that the microcellular β-PP foams exhibiting a cell size of about 8 μm and cell density over 10 8 cells/cm 3 were prepared with a crystalline diameter approximately 5 μm, while PP foams had a rather large cell size approximately 150 μm and low cell density of 10 5 cells/cm 3 with 30 μm crystalline size. As a result, this significant improvement in cell structure as well as the crystalline size lead to a significant increment of 86% for the ductility of β-PP foams. This work offers a facile strategy to prepare injection-molded foams with desirable mechanical properties for their wide range of applications, such as automotive construction and consumer electronics.

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