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载三尖杉酯碱脂质体经抗碳酸酐酶 IX 抗体修饰后肺部给药用于肺癌治疗。

Pulmonary delivery of triptolide-loaded liposomes decorated with anti-carbonic anhydrase IX antibody for lung cancer therapy.

机构信息

School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Hong Kong, China.

School of Biomedical Sciences, Chinese University of Hong Kong, Area 39, CUHK, Shatin, NT, Hong Kong, China.

出版信息

Sci Rep. 2017 Apr 20;7(1):1097. doi: 10.1038/s41598-017-00957-4.

DOI:10.1038/s41598-017-00957-4
PMID:28428618
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5430522/
Abstract

Antibody-decorated liposomes can facilitate the precise delivery of chemotherapeutic drugs to the lung by targeting a recognition factor present on the surface of lung tumor cells. Carbonic anhydrase IX (CA IX) is an enzyme expressed on the surface of lung cancer cells with a restricted expression in normal lungs. Here, we explored the utility of anti-carbonic anhydrase IX (CA IX) antibody, conjugated to the surface of triptolide (TPL)-loaded liposomes (CA IX-TPL-Lips), to promote the therapeutic effects for lung cancer via pulmonary administration. It was found that the CA IX-TPL-Lips significantly improved the cellular uptake efficiency in both CA IX-positive human non-small cell lung cancer cells (A549) and A549 tumor spheroids, resulting in the efficient cell killing compared with free TPL and non-targeted TPL-Lips. In vivo, CA IX-Lips via pulmonary delivery showed specificity and a sustained release property resided up to 96 h in the lung, both of which improved the efficiency of TPL formulations in restraining tumor growth and significantly prolonged the lifespan of mice with orthotopic lung tumors. The results suggest that CA IX-decorated liposomes can potentially be used as an effective therapeutic strategy for lung cancer.

摘要

抗体修饰的脂质体可以通过靶向肺癌细胞表面存在的识别因子，将化疗药物精确递送到肺部。碳酸酐酶 IX（CA IX）是一种在肺癌细胞表面表达的酶，在正常肺部中的表达受到限制。在这里，我们探讨了将抗碳酸酐酶 IX（CA IX）抗体连接到三萜内酯（TPL）负载的脂质体（CA IX-TPL-Lips）表面的用途，通过肺部给药来促进肺癌的治疗效果。结果发现，CA IX-TPL-Lips 显著提高了 CA IX 阳性人非小细胞肺癌细胞（A549）和 A549 肿瘤球体的细胞摄取效率，与游离 TPL 和非靶向 TPL-Lips 相比，导致有效的细胞杀伤。在体内，通过肺部给药的 CA IX-Lips 表现出特异性和长达 96 小时的持续释放特性，这两者都提高了 TPL 制剂抑制肿瘤生长的效率，并显著延长了荷瘤小鼠的寿命。结果表明，CA IX 修饰的脂质体可能可作为治疗肺癌的有效治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/9bad9839bc9b/41598_2017_957_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/dae8d9a8ca0c/41598_2017_957_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/293ce97f0a57/41598_2017_957_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/b76d882dfc08/41598_2017_957_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/cf2f0777abd5/41598_2017_957_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/6718340b0942/41598_2017_957_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/78642646ed0f/41598_2017_957_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/9bad9839bc9b/41598_2017_957_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/dae8d9a8ca0c/41598_2017_957_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/293ce97f0a57/41598_2017_957_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/b76d882dfc08/41598_2017_957_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/cf2f0777abd5/41598_2017_957_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/6718340b0942/41598_2017_957_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/78642646ed0f/41598_2017_957_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ee4/5430522/9bad9839bc9b/41598_2017_957_Fig7_HTML.jpg

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