Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Control Release. 2012 Apr 30;159(2):189-96. doi: 10.1016/j.jconrel.2012.01.038. Epub 2012 Feb 3.
Nano-scaled drug carriers have great potential for the treatment of solid tumors. Nevertheless, hypovascularity and fibrosis in some types of solid tumors have been demonstrated to reduce the penetration and accumulation of nano-scaled drug carriers. Diffuse-type scirrhous gastric cancers present such characteristics as well as frequent metastasis to the lymph nodes; therefore, it remains a great challenge to eradicate scirrhous gastric cancers based on the drug targeting using nanocarriers. Herein, we demonstrated that polymeric micelles with 30-nm diameter incorporating (1,2-diaminocyclohexane)platinum(II) (DACHPt), the parent complex of the anticancer drug oxaliplatin, efficiently penetrated and accumulated in an orthotopic scirrhous gastric cancer model, leading to the inhibition of the tumor growth. Moreover, the elevated localization of systemically injected DACHPt-loaded micelles in metastastic lymph nodes reduced the metastatic tumor growth. These results suggest DACHPt-loaded micelles as a promising nanocarrier for the treatment of scirrhous gastric cancers and their lymphatic metastases.
纳米级药物载体在治疗实体瘤方面具有巨大的潜力。然而,一些类型的实体瘤中的血管生成不足和纤维化已被证明会降低纳米级药物载体的穿透和积累。弥漫型硬癌型胃癌具有这样的特征,并且经常转移到淋巴结;因此,基于纳米载体的药物靶向来根除硬癌型胃癌仍然是一个巨大的挑战。在此,我们证明了直径为 30nm 的包含(1,2-二氨基环己烷)铂(II)(DACHPt)的聚合物胶束,即抗癌药物奥沙利铂的母体复合物,能够有效地穿透和积累在原位硬癌型胃癌模型中,从而抑制肿瘤生长。此外,全身性注射的载 DACHPt 胶束在转移的淋巴结中的定位升高,减少了转移性肿瘤的生长。这些结果表明,载 DACHPt 胶束是治疗硬癌型胃癌及其淋巴转移的一种有前途的纳米载体。