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日本研究人员日前开发出针对胰腺癌的极微小胶囊给药新技术,动物实验已证明这项技术的有效性。
东京大学研究人员报告说,他们利用高分子制造的极微小胶囊封闭化疗药物,注入移植了人体胰腺癌组织的小鼠体内,结果药物被顺利送达癌变部位,成功遏制了癌细胞增殖。
据介绍,肿瘤的毛细血管壁上有孔,微小胶囊随着血流进入血管后,可通过小孔漏到血管外,进入癌细胞释放药物,且胶囊几乎不会进入无关的脏器造成副作用。这项技术已用于卵巢癌等的治疗。但由于胰腺肿瘤血管壁上的孔更小,这种疗法常用的100纳米(1纳米等于十亿分之一米)的胶囊难以漏出,而且血管与癌细胞之间的纤维组织间质会妨碍胶囊的移动,导致药物无法顺利送达。
为此,研究人员开发出只有30纳米的新型胶囊。注射到小鼠体内后,胶囊得以穿过血管壁和间质,聚集到癌细胞周围,持续数天释放药物。研究人员持续观察小鼠16天,没有发现癌细胞增殖。
研究人员说,由于胶囊非常微小,能轻易从胰腺肿瘤的血管中漏出来,且穿透力较强,因此更容易集中到胰腺癌组织周围。新技术将有望提高胰腺癌的治疗效果。
这项研究报告发表在新一期英国《自然—纳米技术》杂志网络版上。(生物谷 Bioon)
doi:10.1038/nnano.2011.166
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PMID:
Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size
H. Cabral,1 Y. Matsumoto,2 K. Mizuno,3 Q. Chen,4 M. Murakami,2 M. Kimura,2 Y. Terada,5 M. R. Kano,6 K. Miyazono,6, 7 M. Uesaka,3, 7 N. Nishiyama2, 7 & K. Kataoka1,
A major goal in cancer research is to develop carriers that can deliver drugs effectively and without side effects. Liposomal and particulate carriers with diameters of ~100 nm have been widely used to improve the distribution and tumour accumulation of cancer drugs, but so far they have only been effective for treating highly permeable tumours. Here, we compare the accumulation and effectiveness of different sizes of long-circulating, drug-loaded polymeric micelles (with diameters of 30, 50, 70 and 100 nm) in both highly and poorly permeable tumours. All the polymer micelles penetrated highly permeable tumours in mice, but only the 30 nm micelles could penetrate poorly permeable pancreatic tumours to achieve an antitumour effect. We also showed that the penetration and efficacy of the larger micelles could be enhanced by using a transforming growth factor-β inhibitor to increase the permeability of the tumours.