A novel peptide enhances therapeutic efficacy of liposomal anti-cancer drugs in mice models of human lung cancer.
A novel peptide enhances therapeutic efficacy of liposomal anti-cancer drugs in mice models of human lung cancer.
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DOI：
10.1371/journal.pone.0004171
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Wu HC
中科院分区：
文献类型：
--
作者：
Chang DK;Lin CT;Wu CH;Wu HC
肺癌是全球癌症相关死亡的主要原因。缺乏肿瘤特异性仍然是有效化疗的主要缺点，并导致剂量限制性毒性。然而，配体介导的药物递送系统应该能够使化疗对肿瘤细胞更具特异性，对正常组织的毒性更小。在这项研究中，我们从噬菌体展示肽库中分离出一种新的肽配体，它与非小细胞肺癌（NSCLC）细胞系结合。靶向噬菌体与几种NSCLC细胞系结合，但不与正常细胞结合。靶向噬菌体和合成肽均能识别NSCLC手术标本，阳性率为75%（27/36）。在携带NSCLC异种移植物的严重联合免疫缺陷（SCID）小鼠中，靶向噬菌体特异性结合肿瘤块。靶向噬菌体的肿瘤归巢能力被同源合成肽抑制，但不被对照或WTY突变肽抑制。当靶向肽偶联到携带阿霉素或长春瑞滨的脂质体时，化疗剂的治疗指数和人肺癌异种移植物小鼠的存活率显著增加。此外，与游离药物相比，靶向脂质体使药物在肿瘤组织中的蓄积增加了5.7倍，并且由于更高浓度的生物可利用的多柔比星而增强了癌细胞凋亡。目前的研究表明，这种肿瘤特异性肽可用于创建在治疗NSCLC中特异性靶向肿瘤细胞的化疗药物，并设计靶向基因转移载体，或者可用于诊断这种恶性肿瘤。
Lung cancer is the leading cause of cancer-related mortality worldwide. The lack of tumor specificity remains a major drawback for effective chemotherapies and results in dose-limiting toxicities. However, a ligand-mediated drug delivery system should be able to render chemotherapy more specific to tumor cells and less toxic to normal tissues. In this study, we isolated a novel peptide ligand from a phage-displayed peptide library that bound to non-small cell lung cancer (NSCLC) cell lines. The targeting phage bound to several NSCLC cell lines but not to normal cells. Both the targeting phage and the synthetic peptide recognized the surgical specimens of NSCLC with a positive rate of 75% (27 of 36 specimens). In severe combined immunodeficiency (SCID) mice bearing NSCLC xenografts, the targeting phage specifically bound to tumor masses. The tumor homing ability of the targeting phage was inhibited by the cognate synthetic peptide, but not by a control or a WTY-mutated peptide. When the targeting peptide was coupled to liposomes carrying doxorubicin or vinorelbine, the therapeutic index of the chemotherapeutic agents and the survival rates of mice with human lung cancer xenografts markedly increased. Furthermore, the targeting liposomes increased drug accumulation in tumor tissues by 5.7-fold compared with free drugs and enhanced cancer cell apoptosis resulting from a higher concentration of bioavailable doxorubicin. The current study suggests that this tumor-specific peptide may be used to create chemotherapies specifically targeting tumor cells in the treatment of NSCLC and to design targeted gene transfer vectors or it may be used one in the diagnosis of this malignancy.
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影响因子：
11.2
作者：
Lee, TY;Wu, HC;Lin, CT
通讯作者：
Lin, CT
DOI：
10.1073/pnas.0504274102
发表时间：
2005-09-06
影响因子：
11.1
作者：
Dharap, SS;Wang, Y;Minko, T
通讯作者：
Minko, T
影响因子：
11.2
作者：
Lee, Tong-Young;Lin, Chin-Tarng;Wu, Han-Chung
通讯作者：
Wu, Han-Chung
影响因子：
4.4
作者：
Colbern, GT;Hiller, AJ;Working, PK
通讯作者：
Working, PK
影响因子：
3.7
作者：
DMello, F;Partidos, CD;Howard, CR
通讯作者：
Howard, CR