Bioavailability and therapeutic efficacy of HER2 scFv-targeted liposomal doxorubicin in a murine model of HER2-overexpressing breast cancer
Bioavailability and therapeutic efficacy of HER2 scFv-targeted liposomal doxorubicin in a murine model of HER2-overexpressing breast cancer
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DOI：
10.1080/10611860802229978
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发表时间：
2008-01-01
影响因子：
4.5
通讯作者：
Allen, T. M.
中科院分区：
文献类型：
--
作者：
Laginha, Kimberley M.;Moase, Elaine H.;Allen, T. M.
包埋在纳米载体如脂质体内部的药物没有治疗活性，即它们不是生物可利用的。为了实现治疗活性，药物从脂质体的释放必须以足以在细胞靶标处实现药物的治疗浓度的速率发生。对于针对内化抗原的配体靶向脂质体，发生脂质体包装的受体介导的内化，并且包封的药物在从溶酶体器胞内释放后变得有活性（生物可利用）。我们已经研究了，在小鼠乳腺癌模型中，阿霉素（DXR）的速率和生物利用度的程度截留在脂质体靶向的单链抗体片段对HER 2/neu抗原，与游离DXR和非靶向脂质体DXR（DOXIL）相比。当使用抗HER 2/neu靶向脂质体时，乳腺癌肿瘤含有最高总水平的DXR和最高水平的生物可利用DXR，并且靶向脂质体也导致最高水平的肿瘤控制。
Drugs that are entrapped in the interior of nanocarriers such as liposomes have no therapeutic activity, i.e. they are not bioavailable. In order to achieve therapeutic activity, drug release from the liposomes must occur at a rate sufficient to achieve therapeutic concentrations of drug at the cellular target. For ligand-targeted liposomes, directed against internalizing antigens, receptor-mediated internalization of the liposome package occurs and the entrapped drugs become active (bioavailable) upon their intracellular release from the lysosomal apparatus. We have examined, in a murine breast cancer model, the rate and the extent of bioavailability of doxorubicin (DXR) entrapped in liposomes targeted by a single-chain antibody fragment against the HER2/neu antigen, in comparison with free DXR and non-targeted liposomal DXR (DOXIL). Breast cancer tumors contained the highest total levels of DXR and the highest levels of bioavailable DXR when anti-HER2/neu-targeted liposomes were used, and the targeted liposomes also resulted in the greatest level of tumor control.