叶酸受体介导米托蒽醌白蛋白纳米粒的体内分布及药效学研究

Study on Biodistribution and Pharmacodynamics of Folate Receptor-Mediated Mitoxantrone-Loaded Albumin Nanoparticles

目的考察叶酸偶联米托蒽醌白蛋白纳米粒(MTO-BSANP-folate)在荷瘤裸鼠体内分布特征及抑瘤情况。方法以荷SKOV3人卵巢肿瘤细胞裸鼠为模型,考察了MTO-BSANP-folate对荷瘤裸鼠肿瘤生长情况的影响,并与米托蒽醌白蛋白纳米粒(MTO-BSANP)及米托蒽醌溶液(MTO-sol)进行比较。采用HPLC研究静脉给药后各实验组米托蒽醌的体内分布情况。结果尾静脉给予MTO-BSANP-folate的荷瘤裸鼠肿瘤生长最为缓慢,抑瘤率最高。体内分布实验结果表明,MTO-BSANP-folate在肿瘤的分布高于MTO-BSANP及MTO-sol。结论叶酸偶联米托蒽醌白蛋白纳米粒是一种有潜力的抗肿瘤药物的载体,可靶向于高表达叶酸受体的肿瘤。

OBJECTIVE To investigate the biodistribution and pharmacodynamics of folate-conjugated mitoxantrone-loaded albu- min nanoparticles （MTO-BSANP-folate） in vivo. METHODS MTO-BSANP-folate, mitoxantrone-loaded albumin nanoparticles （MTO-BSANP） and mitoxantrone solution （MTO-sol） was injected respectively into the tail vein of the BALB/c nude mice bearing transplanted SKOV3 ovarian carcinoma at specific intervals. Tumor dimensions, tumor growth inhibitory rates of each group were respectively evaluated. And the biodistribution of MTO-sol, MTO-BSANP and MTO-BSANP-folate in the organs and tumors was determined by HPLC. RESULTS The tumor growth in mice given MTO-BSANP-folate was slowest in three mitoxantrone treatment groups. The tumor growth inhibitory rates by MTO-sol, MTO-BSANP and MTO-BSANP-folate were 63. 10%, 67.85% and 84.5% respectively. When being given MTO-BSANP-folate, higher concentrations of mitoxantrone were obtained in tumor as compared to MTO-BSANP and MTO-sol. CONCLUSION MTO-BSANP-folate has the potential for treating solid tumors with overexpressed folate receptors.