Li Zhao, Sun Liping, Lu Zaijun, Su Xuantao, Yang Qifeng, Qu Xun, Li Li, Song Kun, Kong Beihua
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
School of Chemistry and Chemical Engineering, Shandong University, Jinan, Shandong 250012, P.R. China.
Int J Oncol. 2015 Sep;47(3):1070-6. doi: 10.3892/ijo.2015.3079. Epub 2015 Jul 10.
Nanoparticles are promising novel drug delivery carriers that allow tumor targeting and controlled drug release. In the present study, we prepared poly butyl-cyanoacrylate nanoparticles (PBCA-NP) entrapped with hypocrellin B (HB) to improve the effect of photodynamic therapy (PDT) in ovarian cancer. An ovarian cancer ascites model using Fischer 344 rats and PBCA-NP entrapped with HB (HB-PBCA-NP) were formed successfully. The pharmacodynamic characteristics and biodistribution of the HB-PBCA-NP system were evaluated by comparison with HB dimethyl sulfoxide (HB-DMSO) and testing at various time-points following intraperitoneal drug administration. HB-PBCA-NP-based PDT combined with cytoreductive surgery was then administrated to the tumor-bearing animals. Kaplan-Meier survival analysis was performed to assess the therapeutic effect of the nanoparticle system. The serum HB concentration peaked 4 h after drug administration in the nanoparticle system, and 1 h with HB-DMSO. The peak exposure time of tumor tissues was also extended (4 vs. 2 h), and PBCA-NP remained present for much longer than HB-DMSO. Although PDT combined with surgery prolonged the survival time significantly compared with surgery alone (84 days, P<0.05), there was no significant difference in the survival time of animals that received either HB-PBCA-NP- or HB-DMSO-based PDT after cytoreductive surgery (99 vs. 95 days, P=0.293). PBCA-NP exhibited potential advantages in controlled drug release and tumor targeting, which was beneficial for HB-based PDT. PDT combined with surgery prolonged the survival time, suggesting that this might be an alternative treatment option for ovarian cancer.
纳米颗粒是很有前景的新型药物递送载体,可实现肿瘤靶向和药物控释。在本研究中,我们制备了包裹竹红菌素B(HB)的聚氰基丙烯酸丁酯纳米颗粒(PBCA-NP),以提高光动力疗法(PDT)治疗卵巢癌的效果。成功构建了使用Fischer 344大鼠的卵巢癌腹水模型以及包裹HB的PBCA-NP(HB-PBCA-NP)。通过与HB二甲基亚砜(HB-DMSO)比较并在腹腔给药后的不同时间点进行检测,评估了HB-PBCA-NP系统的药效学特征和生物分布。然后对荷瘤动物实施基于HB-PBCA-NP的PDT联合肿瘤细胞减灭术。进行Kaplan-Meier生存分析以评估纳米颗粒系统的治疗效果。纳米颗粒系统给药后血清HB浓度在4小时达到峰值,而HB-DMSO组在1小时达到峰值。肿瘤组织的峰值暴露时间也延长了(4小时对2小时),并且PBCA-NP的存在时间比HB-DMSO长得多。虽然与单纯手术相比,PDT联合手术显著延长了生存时间(84天,P<0.05),但在肿瘤细胞减灭术后接受基于HB-PBCA-NP或HB-DMSO的PDT的动物的生存时间没有显著差异(99天对95天,P=0.293)。PBCA-NP在药物控释和肿瘤靶向方面显示出潜在优势,这有利于基于HB的PDT。PDT联合手术延长了生存时间,表明这可能是卵巢癌的一种替代治疗选择。