Integrin αvβ3 is a promising target for integrin-rich tumor and neovascular. In the present study, we prepared a doxorubicin (DOX)-loaded liposome of which the surface was decorated with PEG and a novel αvβ3 targeting peptide of P1c. The in vitro targeting efficiency was evaluated in αvβ3-positive (U87MG) and -negative (MCF-7) tumor cells by flow cytometry and laser confocal scanning microscopy. The in vivo therapeutic effects were evaluated in the glioblastoma U87MG-tumor bearing mouse model. The results indicated that the prepared liposomes showed mean sizes of 131.2 and 128.4 nm in diameter for P1c-modified targeting liposomes (P1c-DOXL) and non-targeting liposomes (DOXL), respectively. The DOX encapsulation efficiencies were more than 95% in both types of liposomes. The conjugation ratio for P1c decoration was 66.8%. The flow cytometry and confocal laser-scanning microscopy experiments consistently showed that the intracellular fluorescence intensity of the P1c-modified targeted liposome group was stronger than that of the non-targeted liposome group (P < 0.05) in U87MG cells. In vivo results revealed that compared with DOX or DOXL treatment, P1c-DOXL dramatically reduced tumor growth (P < 0.05) and tumor angiogenesis while much lower hepatotoxicity was observed. P1c-modified targeting liposome exhibited sustained release, enhancing the antitumor effect of DOX through targeting tumor cells and neovascular where integrin αvβ3 was overexpressed. The results indicated that P1c might be promising for active targeting delivery in cancer therapy.

中文翻译：

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在体外和体内靶向表达 αvβ3 的肿瘤细胞的 P1c 肽修饰脂质体

整合素αvβ3是富含整合素的肿瘤和新生血管的有希望的靶标。在本研究中，我们制备了一种负载多柔比星 (DOX) 的脂质体，其表面装饰有 PEG 和一种新型的 P1c αvβ3 靶向肽。通过流式细胞术和激光共聚焦扫描显微镜在 αvβ3 阳性 (U87MG) 和阴性 (MCF-7) 肿瘤细胞中评估体外靶向效率。体内_在胶质母细胞瘤 U87MG 荷瘤小鼠模型中评估治疗效果。结果表明，对于 P1c 修饰的靶向脂质体 (P1c-DOXL) 和非靶向脂质体 (DOXL)，制备的脂质体的平均直径分别为 131.2 和 128.4 nm。两种脂质体的 DOX 封装效率均超过 95%。P1c修饰的共轭率为66.8%。流式细胞仪和共聚焦激光扫描显微镜实验一致表明，在U87MG细胞中，P1c修饰靶向脂质体组的细胞内荧光强度强于非靶向脂质体组（P < 0.05）。体内结果显示，与 DOX 或 DOXL 治疗相比，P1c-DOXL 显着降低了肿瘤生长（P < 0.05）和肿瘤血管生成，同时观察到更低的肝毒性。P1c修饰的靶向脂质体表现出持续释放，通过靶向整合素αvβ3过表达的肿瘤细胞和新生血管来增强DOX的抗肿瘤作用。结果表明，P1c 可能有望用于癌症治疗中的主动靶向递送。