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抗人肝癌单克隆抗体HAb18偶联纳米球的抗肿瘤作用

[Antitumor effect of nanospheres coupled with the anti-human liver cancer monoclonal antibody HAb18].

作者信息

Kan He-ping, Liu Zheng-jun, Tan Yang-fa, Lin Yi-xiong, Li Chun-fang, Zhou Jie

机构信息

Department of Hepatobilliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2008 Aug;28(8):1503-5.

Abstract

OBJECTIVE

To prepare nanospheres coupled with the anti-human liver cancer monoclonal antibody HAb18 and evaluate its immunoreactivity and antitumor effects.

METHODS

The nanosphere coupled with the antibody was prepared by intermolecular cross-linking the anti-human liver cancer monoclonal antibody, HAb18, with human serum albumin nanospheres containing ADM [termed HAS(ADM)-NS] via a new hetero-bifunctional cross-linker SPDP. Condensation test and immunofluorescence assay were used to evaluate the immunoreactivity of the nanospheres, and specific binding of HAb18-HAS(ADM)-NS with liver cancer cell line SMMC-7721 was observed with optical and electron microscopes. The specific cytotoxic effects on the target cells were evaluated in vitro by MTT assay. HAb18-HAS(ADM)-NS, HAS(ADM)-NS and ADM were injected separately into nude mice bearing human liver carcinoma to evaluate the inhibitory activity of HAb18-HAS(ADM)-NS in vivo.

RESULTS

The immunoreactivity of HAb18-HAS(ADM)-NS was well preserved. HAb18-HAS(ADM)-NS could bind specifically with the SMMC-7721 cells. The IC(50) of HAb18-HAS(ADM)-NS against SMMC-7721 cells was 44.6 microg/ml, lower than that of HAS(ADM)-NS (345.5 microg/ml) and ADM (365.5 microg/ml). The inhibition rate of HAb18-HAS(ADM)-NS on the growth of liver cancer xenografts was significantly higher than that of HAS(ADM)-NS and ADM (P<0.001).

CONCLUSION

HAb18-HAS(ADM)-NS has immunoreactivity and can actively and specifically target the liver cancer cells. The antitumor activity of HAb18-HAS(ADM)-NS is significantly higher than that of HAS(ADM)-NS and ADM.

摘要

目的

制备偶联抗人肝癌单克隆抗体HAb18的纳米球,并评价其免疫反应性和抗肿瘤作用。

方法

采用新型异双功能交联剂SPDP,通过分子间交联抗人肝癌单克隆抗体HAb18与含阿霉素的人血清白蛋白纳米球[称为HAS(ADM)-NS],制备偶联抗体的纳米球。采用凝聚试验和免疫荧光分析法评价纳米球的免疫反应性,用光镜和电镜观察HAb18-HAS(ADM)-NS与肝癌细胞系SMMC-7721的特异性结合。采用MTT法体外评价其对靶细胞的特异性细胞毒作用。将HAb18-HAS(ADM)-NS、HAS(ADM)-NS和阿霉素分别注射到荷人肝癌裸鼠体内,评价HAb18-HAS(ADM)-NS的体内抑制活性。

结果

HAb18-HAS(ADM)-NS的免疫反应性得到良好保留。HAb18-HAS(ADM)-NS能与SMMC-7721细胞特异性结合。HAb18-HAS(ADM)-NS对SMMC-7721细胞的半数抑制浓度(IC50)为44.6μg/ml,低于HAS(ADM)-NS(345.5μg/ml)和阿霉素(365.5μg/ml)。HAb18-HAS(ADM)-NS对肝癌异种移植瘤生长的抑制率明显高于HAS(ADM)-NS和阿霉素(P<0.001)。

结论

HAb18-HAS(ADM)-NS具有免疫反应性,能主动、特异性地靶向肝癌细胞。HAb18-HAS(ADM)-NS的抗肿瘤活性明显高于HAS(ADM)-NS和阿霉素。

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