Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Biomaterials. 2011 Nov;32(33):8548-54. doi: 10.1016/j.biomaterials.2011.07.067. Epub 2011 Aug 16.
Peritoneal metastasis is a major cause of morbidity and mortality in ovarian cancer. While intraperitoneal chemotherapy and radiotherapy have shown favorable clinical results, both are limited by their non-targeted nature. We aimed to develop a biologically targeted nanoparticle therapeutic for the treatment of ovarian cancer peritoneal metastasis. Folate-targeted nanoparticles encapsulating chemotherapy and/or radiotherapy were engineered. Paclitaxel (Ptxl) was used as the chemotherapeutic and yittrium-90 ((90)Y) was employed as the therapeutic radioisotope. Folate was utilized as the targeting ligand as most ovarian cancers overexpress the folate receptor. Nanoparticle characterization studies showed monodispersed particles with controlled Ptxl release. Folate targeting ligand mediated the uptake of NPs into tumor cells. In vitro efficacy studies demonstrated folate-targeted NPs containing chemoradiotherapy was the most effective therapeutic compared to folate-targeted NPs containing a single therapeutic or any non-targeted NP therapeutics. In vivo efficacy studies using an ovarian peritoneal metastasis model showed that folate-targeted NP therapeutics were significantly more effective than non-targeted NP therapeutics. Among the folate-targeted therapeutics, the NP containing chemoradiotherapy appeared to be the most effective. Our results suggest that folate-targeted nanoparticles containing chemoradiotherapy have the potential as a treatment for ovarian peritoneal metastasis.
腹膜转移是卵巢癌发病率和死亡率的主要原因。虽然腹腔内化疗和放疗显示出良好的临床效果，但两者都受到其非靶向性质的限制。我们旨在开发一种针对卵巢癌腹膜转移的生物靶向纳米颗粒治疗方法。设计了叶酸靶向纳米颗粒，封装化疗药物和/或放疗药物。紫杉醇（Ptxl）用作化疗药物，钇-90（(90)Y）用作治疗放射性同位素。叶酸被用作靶向配体，因为大多数卵巢癌过度表达叶酸受体。纳米颗粒表征研究表明，纳米颗粒具有单分散性和控制的 Ptxl 释放。叶酸靶向配体介导 NPs 被肿瘤细胞摄取。体外疗效研究表明，与含有单一治疗药物或任何非靶向 NP 治疗药物的叶酸靶向 NPs 相比，含有化疗和放疗的叶酸靶向 NPs 是最有效的治疗方法。在卵巢腹膜转移模型的体内疗效研究中，叶酸靶向 NP 治疗药物明显比非靶向 NP 治疗药物更有效。在叶酸靶向治疗药物中，含有化疗和放疗的 NP 似乎最有效。我们的研究结果表明，含有化疗和放疗的叶酸靶向纳米颗粒具有治疗卵巢腹膜转移的潜力。
