给药方法新突破：吸入性纳米药物有效治疗肺癌

由俄勒冈州立大学、罗格斯大学和新泽西癌症研究中心的研究人员发明了一种新型的吸入性化疗方法来治疗肺癌，在体外和动物试验的结果都显示该方法能降低化疗药物对全身其他系统的伤害，同时能显著增强肺癌的治疗效果，相关研究发表在Journal of Controlled Release期刊上。

新方法结合微小纳米颗粒、抗癌药物和抑制耐药性的干扰RNA三要素，这些优势的整合作用导致了试验动物体内肺癌的消失，从而推动纳米医学研究的进展。

肺癌是目前男性和女性的首要杀手，尽管手术治疗取得了长足的进步，化疗依然是肺癌治疗的主要方法。不过化疗受到药物的毒性作用和如何将药物难以传递到肺部的种种限制。“肺癌导致的伤害通常不仅仅在局部，这就是为何化疗起重要作用的原因所在。”论文作者Taratula说。“但是，化疗药物毒性大，如果采用传统的静脉给药方式会导致器官的伤害和严重的毒副作用。”

他补充道，吸入性给药系统是一个更为有效的方式，能够最大程度的针对癌细胞，其他化疗方式只是抑制肿瘤，这种给药方式貌似可以消灭他们。而据研究人员称，目前已经申请了本技术的专利，在进入人体临床试验之前将需要更多的测试。

“纳米结构脂质给药系统”是吸入性治疗肺癌的有效成分，比灰尘都小很多的给药系统非常易于吸入给药和黏附到癌症细胞上，主要是用来传递抗癌药物，不过也可以携带siRNA序列，使得癌症细胞更易于攻击。

肿瘤细胞通常有两种耐药方式：“药物泵耐药”将药物从细胞中排出；“非药物泵耐药”防止细胞死亡。该系统中使用siRNA的目的是消除这两种耐药性，使得癌细胞对药物敏感。通过吸入的方式给药，可以避免静脉注射化疗药物导致的降解。药物以完整的方式到达肺部作用部位，同时减少各种副作用。

在传统的化疗给药方式治疗肺癌时，药物会在肝、肾和脾脏中聚集，只有很少一部分会到达肺部。在本研究中，吸入给药系统有83%的药物到达作用器官，而注射给药只有23%到达作用器官。

原文链接：

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Surface-engineered targeted PPI dendrimer for efficient intracellular and intratumoral siRNA delivery

Low penetration ability of Small Interfering RNA (siRNA) through the cellular plasma membrane combined with its limited stability in blood, limits the effectiveness of the systemic delivery of siRNA. In order to overcome such difficulties, we constructed a nanocarrier-based delivery system by taking advantage of the lessons learned from the problems in the delivery of DNA. In the present study, siRNA nanoparticles were first formulated with Poly(Propyleneimine) (PPI) dendrimers. To provide lateral and steric stability to withstand the aggressive environment in the blood stream, the formed siRNA nanoparticles were caged with a dithiol containing cross-linker molecules followed by coating them with Poly(Ethylene Glycol) (PEG) polymer. A synthetic analog of Luteinizing Hormone-Releasing Hormone (LHRH) peptide was conjugated to the distal end of PEG polymer to direct the siRNA nanoparticles specifically to the cancer cells. Our results demonstrated that this layer-by-layer modification and targeting approach confers the siRNA nanoparticles stability in plasma and intracellular bioavailability, provides for their specific uptake by tumor cells, accumulation of siRNA in the cytoplasm of cancer cells, and efficient gene silencing. In addition, in vivo body distribution data confirmed high specificity of the proposed targeting delivery approach which created the basis for the prevention of adverse side effects of the treatment on healthy organs.



来源：生物探索