Inhibiting Tumor Growth by Targeting Tumor Vasculature with Galectin-1 Antagonist Anginex Conjugated to the Cytotoxic Acylfulvene, 6-Hydroxylpropylacylfulvene
Inhibiting Tumor Growth by Targeting Tumor Vasculature with Galectin-1 Antagonist Anginex Conjugated to the Cytotoxic Acylfulvene, 6-Hydroxylpropylacylfulvene
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DOI：
10.1021/bc900287y
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发表时间：
2010-01-01
影响因子：
4.7
通讯作者：
Mayo, Kevin H.
中科院分区：
文献类型：
--
作者：
Dings, Ruud P. M.;Van Laar, Emily S.;Mayo, Kevin H.
治疗药物的靶向递送有望成为治疗癌症的规范。在这里，我们将细胞毒性剂6-羟丙基酰基富烯（HPAF）与anginex结合，anginex是一种靶向半乳糖凝集素-1的肽，在肿瘤血管的内皮细胞中高度表达。在小鼠的人卵巢癌模型中，缀合物比单独的等效剂量的任一化合物更好地抑制肿瘤生长。肿瘤组织免疫荧光显示，偶联物与亲本anginex一样，选择性靶向肿瘤血管并抑制肿瘤血管生成。缀合物的活性增加进一步表明，当与心绞痛连接时，HPAF保留至少一些其正常的细胞毒性活性。更重要的可能是观察到缀合物消除了用HPAF治疗的明显全身毒性。这项工作有助于临床上针对癌症的肿瘤血管靶向剂的开发。
Targeted delivery of therapeutic drugs promises to become the norm to treat cancer. Here, we conjugated the cytotoxic agent 6-hydroxypropylacylfulvene (HPAF) to anginex, a peptide that targets galectin-1, which is highly expressed in endothelial Cells of tumor vessels. In a human ovarian cancer model in mice, the conjugate inhibited tumor growth better than equivalent doses of either compound alone. Immunofluorescence oil tumor tissue demonstrated that the conjugate, like parent anginex, selectively targeted tumor vasculature and inhibited tumor angiogenesis. Increased activity from the conjugate further suggests that HPAF retains at least some of its normal cytotoxic activity when linked to anginex. More importantly perhaps is the observation that the conjugate abrogates apparent systemic toxicity from treatment with HPAF This work contributes to the development of tumor vascular targeting agents against cancer in the clinic.