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Presently, there are no few anticancer drugs that have been used clinically due to their poor targeting ability, short half-life period, non-selective distributions, generation of vasculogenic mimicry (VM) channels, high metastasis, and high recurrence rate. This study aimed to explore the effects of R 8 modified epirubicin-dihydroartemisinin liposomes that could target non-small-cell lung cancer (NSCLC) cells, destroy VM channels, inhibit tumor metastasis, and explain the possible underlying mechanism. In vitro assays indicated that R 8 modified epirubicin-dihydroartemisinin liposomes with ideal physicochemical characteristics could exhibit not only powerful cytotoxicity on A549 cells, but also the effective suppression of VM channels and tumor metastasis. Mechanistic studies manifested that R 8 modified epirubicin-dihydroartemisinin liposomes could down-regulate the levels of VE-Cad, TGF-b1, MMP-2, and HIF-1a. In vivo assays indicated that R 8 modified epirubicin-dihydroartemisinin liposomes could both increase the selective accumulation of chemotherapeutic drugs at tumor sites and show a targeting conspicuous of antitumor efficacy. In conclusion, the R 8 modified epirubicin-dihydroartemisinin liposomes prepared in this study provide a treatment strategy with high efficiency for NSCLC.

| 621 wileyonlinelibrary.com/journal/cas | INTRODUC TI ONLung cancer is one of the most common malignancies and a leading cause of cancer-related death worldwide. 1 Among all lung cancers, approximately 85% are non-small cell lung cancer (NSCLC), for which morbidity is significantly higher than for small cell lung cancer. 2 In the past decade, targeted therapy, immunotherapy, and similar approaches rapidly developed to become the new treatment modalities for NSCLC. Despite recent developments and improvements in diagnosis and treatment, prospects for patients with NSCLC are dismal and the 5-year overall survival rate is only 15%-18%. 3,4 Rapid growth and metastasis are basic biological characteristics of malignant tumors, including NSCLC. 5 It is well known that angiogenesis plays a key role in cancer growth and metastasis. Anti-angiogenesis treatment has evolved to achieve encouraging results, but despite the widespread application of anti-angiogenic drugs, they have not attained satisfactory efficacy. [6][7][8] This means that alternative nutrient supply channels support tumor growth.Vasculogenic mimicry (VM) is defined as formation of vascu- lar-like structures lined with tumor cells without the presenceThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractChemotherapy for non-small cell lung cancer (NSCLC) is far from satisfactory, mainly due to poor targeting of antitumor drugs and self-adaptations of the tumors.Angiogenesis, vasculogenic mimicry (VM) channels, migration, and invasion are the main ways for tumors to obtain nutrition. Herein, RPV-modified epirubicin and dioscin co-delivery liposomes were successfully prepared. These liposomes showed ideal physicochemical properties, enhanced tumor targeting and accumulation in tumor sites, and inhibited VM channel formation, tumor angiogenesis, migration and invasion. The liposomes also downregulated VM-related and angiogenesis-related proteins in vitro. Furthermore, when tested in vivo, the targeted co-delivery liposomes increased selective accumulation of drugs in tumor sites and showed extended stability in blood circulation. In conclusion, RPV-modified epirubicin and dioscin co-delivery liposomes showed strong antitumor efficacy in vivo and could thus be considered a promising strategy for NSCLC treatment. K E Y W O R D Sangiogenesis, cell-penetrating peptide, co-delivery liposome, non-small cell lung cancer, vasculogenic mimicry

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The deformation behavior of isotactic polypropylene (iPP) spherulites with uniaxial stretching was investigated at different drawing temperatures via in situ polarized optical microscope (POM) observation. The iPP spherulites were prepared by two procedures: cooled to the room temperature from melt and annealed at 135, 140, and 145°C for 3 h. It was found that the crystallization conditions dominate the crystalline morphology and even the tensile properties of iPP. For iPP which crystallized during cooling progress, the spherulites were imperfect and the boundaries of the spherulites were diffuse, displaying good toughness at various drawing temperatures. For iPP annealed at high temperatures displayed the brittle fracture‐modes and the crack happened between spherulites, which due to the large and perfective spherulites have thick lamellas and weak connection at interspherulitic boundary. The shape and size of the iPP spherulites formed at 140 and 145°C are affected with uniaxial stretching till to the fracture of the samples at different drawing temperatures. The spherulites obtained at 135°C are deformed along the drawing direction at 100°C but not affected at low drawing temperatures, indicating the toughness increased with the increase of the drawing temperatures. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers