纳米羟基磷灰石诱导的体外特异性抗肿瘤免疫反应研究

Study on In Vitro Specificity Anticancer Immune Response Induced by Nanometer Hydroxyapatite

探讨了纳米羟基磷灰石(hydroxyapatite,HAp)作为肿瘤免疫治疗佐剂或抗原载体的可行性。利用水热法合成棒状、长径200~300nm、短径30~50nm的纳米HAp,体外降解实验表明HAp 90d的降解率可达30%。以人乳腺癌细胞裂解蛋白为肿瘤抗原,利用HAp负载该肿瘤抗原并刺激人外周血单个核细胞来源的树突细胞,将刺激后的树突细胞与同源淋巴细胞共培养,分离共培养后的同源淋巴细胞,并检测其对人非小细胞肺癌细胞A549、人肝癌细胞Huh-7、人乳腺癌细胞MCF-7、人乳腺正常细胞(Hs578Bst)的生长抑制效果。结果表明:所制备的纳米HAp无纳米毒性且生物相容性良好;HAp可显著增强人树突细胞对肿瘤抗原的吞噬作用,同时诱导同源淋巴细胞产生显著的抗原特异性免疫反应,杀伤率可达40%以上。

This study explores the feasibility of using hydroxyapatite（HAp）nanoparticles as adjuvant or antigen carrier in cancer immunotherapy.Rod-shaped HAp nanoparticles 200~300nm in length and 30~50nm in width were synthesized with hydrothermal method.Degradation experiment in vitro indicates that the degradation rate of Hap can reach 30%in 90 days.With human breast cancer cell ce-cropins as tumor antigen,Hap was made use to carry the tumor antigen and stimulate dendritic cells from peripheral blood mononuclear cells,the stimulated dendritic cells were co-cultured with homologous lymphocytes,the co-cultured homologous lymphocytes were separated,and the growth inhibition effect of the co-cultured homologous lymphocytes on A549,Huh-7,MCF-7and Hs578 Bst was tested.The results show that the prepared HAp nanoparticles have no nanotoxicity and are of high biocompatibility;HAp can significantly enhance the phagocytosis of dendritic cells on tumor antigens,and induce homologous lymphocytes to generate significant antigen-specific antitumor immunity,which a killing rate up to above 40%.