受体介导米托蒽醌白蛋白纳米粒肿瘤细胞靶向性研究

Tumor Cell Targetability of Folate Receptor-mediated Mitoxantrone Albumin Nanoparticles

目的研究叶酸偶联米托蒽醌白蛋白纳米粒(MTO-BSANP-FOLATE)的肿瘤细胞靶向性。方法采用去溶剂化法制备白蛋白纳米粒,采用叶酸活性酯在微碱性条件下与白蛋白纳米粒表面的活性氨基偶联制备叶酸偶联白蛋白纳米粒,再将其与米托蒽醌混合,戊二醛固化,制备MTO-BSANP-FOLATE。采用3HTDR掺入法和流式细胞术对其肿瘤细胞靶向性进行评价。结果所制备的MTO-BSANP-FOLATE包封率为(96.55±0.96)%,载药量为(9.66±0.10)%。3HTDR掺入法和流式细胞术结果表明MTO-BSANP-FOLATE组的肿瘤细胞抑制率及凋亡率均高于MTO-BSANP。结论MTO-BSANP-FOLATE可通过肿瘤细胞高表达的叶酸受体靶向于肿瘤细胞。

Objective To study the tumor cell targetability of folate-conjugated mitoxantone-loaded albumin nanoparticles （MTO-BSANP-folate）. Methods Bovine albumin nanoparticles were prepared by desolvation method. The activated folic acid （N-hydroxysuccinimide ester of folic acid） was conjuated to the surface of BSANP via the amino groups. The MTO-BSANP-folate was prepared by mixing folate-conjugated albumin nanoparticles with mitoxantrone and then cross-linked by glutaraldehyde. SHTdR and flow cytometry were used to evaluate the targetability of MTO-BSANP-folate. Results The encapsulation rate of folate-conjugated mitoxantrone albumin nanoparticles was （96.55±0. 96）% and the drug loading was （9.66±0. 10）%. The results of SHTdR showed that the efficacy of MTO-BSANP-folate in killing SKOV3 cells was higher than that of MTO- BSANP-folate, and the results of flow cytometry showed that the apoptosis-promoting effect of MTO-BSANP-folate was 3.5-4.5 times higher than that of MTO-BSANP. Conclusion MTO-BSANP-folate could be targeted, via folate receptor, to the tumor cells rich in folate receptors.