Enhanced Antitumor Response Mediated by the Codelivery of Paclitaxel and Adenoviral Vector Expressing IL-12
Enhanced Antitumor Response Mediated by the Codelivery of Paclitaxel and Adenoviral Vector Expressing IL-12
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紫杉醇和表达 IL-12 的腺病毒载体共同传递介导的增强抗肿瘤反应
DOI：
10.1021/mp300602j
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发表时间：
2013-05-01
影响因子：
4.9
通讯作者：
Sun, Xun
中科院分区：
文献类型：
--
作者：
Cao, Linjie;Zeng, Qin;Sun, Xun
使用细胞毒性药物和适当的细胞因子的化学免疫疗法为治疗肿瘤性疾病提供了一种有前途的方法。鉴于此，本研究将紫杉醇（PTX）和编码鼠白细胞介素-12（Ad 5-mIL-12）的腺病毒（Ad 5-mIL-12）复合到阴离子脂质体（AL）中，构建了一种新型的共递送系统（AL/Ad 5/PTX）。首先，通过使用钙诱导相变将Ad 5掺入阴离子PTX脂质体中来制备AL/Ad 5/PTX复合物。其次，研究了AL/Ad 5/PTX的粒径分布和zeta电位。第三，体外转导实验结果表明，PTX引入AL/Ad-luc或AL/Ad 5-mIL-12中，在B16细胞中的基因转导效率显著高于裸Ad 5或AL/Ad复合物，而在A549细胞中没有可比性。最后，建立荷黑色素瘤小鼠模型以评估抗肿瘤作用。与用AL/Ads-mIL-12或AL/PTX治疗的小鼠相比，在用AL/Ad 5-mIL-12/PTX治疗的小鼠中观察到肿瘤生长抑制和延长的存活时间，伴随着血清或肿瘤部位中mIL-12或干扰素-γ（IFN-γ）表达水平的增加。总之，这些结果表明，将Ad 5-mIL-12和PTX共同递送到AL中可能是治疗黑色素瘤的相对有效的策略。
It has been well-established that chemo-immunotherapy using cytotoxic drugs and appropriate cytokines offers a promising approach for the treatment of neoplastic diseases. In view of this, to improve melanoma treatment effect, our study developed a new codelivery system (AL/Ad5/PTX) that paclitaxel (PTX) and adenovirus encoding for murine interleukin-12 (Ad5-mIL-12) were incorporated into anionic liposomes (AL). First, AL/Ad5/PTX complexes were prepared by incorporating Ad5 into anionic PTX liposomes using calcium induced phase change. Second, the size distribution and zeta potential of AL/Ad5/PTX were investigated. Third, the results of in vitro transduction assays showed that PTX introduced into AL/Ad-luc or AL/Ad5-mIL-12 highly enhanced gene transduction efficiency in B16 cells than naked Ad5 or AL/Ad complexes while it had no comparability in A549 cells. Finally, a melanoma-bearing mouse model was established to assess the antitumor effect. Tumor growth inhibition and prolonged survival time, accompanied by increased mIL-12 or interferon-gamma (IFN-gamma) expression levels in serum or tumor sites, were observed in mice treated with AL/Ad5-mIL-12/PTX, as compared with those treated with either AL/Ads-mIL-12 or AL/PTX. In conclusion, these results suggested that codelivery of Ad5-mIL-12 and PTX incorporated into AL could be a relatively efficient strategy for the treatment of melanoma.