Mastria Eric M, Chen Mingnan, McDaniel Jonathan R, Li Xinghai, Hyun Jinho, Dewhirst Mark W, Chilkoti Ashutosh
Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States.
Department of Biosystems and Biomaterials Science and Engineering, Seoul National University, Seoul 151-742, Republic of Korea.
J Control Release. 2015 Jun 28;208:52-8. doi: 10.1016/j.jconrel.2015.01.033. Epub 2015 Jan 28.
Drug delivery vehicles are often assessed for their ability to control primary tumor growth, but the outcome of cancer treatment depends on controlling or inhibiting metastasis. Therefore, we studied the efficacy of our genetically encoded polypeptide nanoparticle for doxorubicin delivery (CP-Dox) in the syngeneic metastatic murine models 4T1 and Lewis lung carcinoma. We found that our nanoparticle formulation increased the half-life, maximum tolerated dose, and tumor accumulation of doxorubicin. When drug treatment was combined with primary tumor resection, greater than 60% of the mice were cured in both the 4T1 and Lewis lung carcinoma models compared to 20% treated with free drug. Mechanistic studies suggest that metastasis inhibition and survival increase were achieved by preventing the dissemination of viable tumor cells from the primary tumor.
药物递送载体通常根据其控制原发性肿瘤生长的能力进行评估，但癌症治疗的结果取决于控制或抑制转移。因此，我们研究了我们的基因编码多肽纳米颗粒（CP-Dox）在同基因转移性小鼠模型4T1和Lewis肺癌中递送阿霉素的疗效。我们发现，我们的纳米颗粒制剂增加了阿霉素的半衰期、最大耐受剂量和肿瘤蓄积量。当药物治疗与原发性肿瘤切除相结合时，在4T1和Lewis肺癌模型中，超过60%的小鼠被治愈，而游离药物治疗组的治愈率为20%。机制研究表明，通过阻止活肿瘤细胞从原发性肿瘤中扩散，实现了转移抑制和生存率提高。
