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Emerging nanodelivery strategies of RNAi molecules for colon cancer therapy: Preclinical developments

机译:RNAi分子用于结肠癌治疗的新兴纳米递送策略:临床前发展

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Although local colonic delivery is achievable through several strategies, colon cancer is still considered one of the leading causes of death worldwide. Failure of chemotherapeutics to exhibit efficient anticancer activity might be attributed to the development of multidrug resistance (MDR) mechanisms including the overexpression of certain oncogenes such as MDR1/P-gp. One of the major reasons for the shortcoming of P-gp inhibitors in clinic is the nonspecific distribution of them to nontarget organs, which leads to reduced elimination and increased toxicity of its substrates including anticancer agents. Numerous studies have demonstrated the effectiveness of gene-silencing approaches in reversing the P-gp-mediated MDR. However, none have reached clinical trials yet. Several drug-delivery systems have been investigated primarily to address P-gp and the observed improved anticancer efficacy suggests that nanomedicine provides new opportunities to overcome MDR in cancer. In this review, novel therapeutic strategies for colon cancer therapy will be discussed in the context of P-gp inhibition by low-molecular-weight agents and RNAi molecules.
机译:尽管可以通过多种策略实现局部结肠递送,但结肠癌仍被认为是全球范围内主要的死亡原因之一。化学治疗药物未能显示出有效的抗癌活性可能归因于多药耐药性(MDR)机制的发展,包括某些癌基因如MDR1 / P-gp的过表达。 P-gp抑制剂在临床上的不足的主要原因之一是它们在非靶器官中的非特异性分布,这导致其包括抗癌药的底物的消除减少和毒性增加。大量研究表明,基因沉默方法可逆转P-gp介导的MDR。但是,尚无临床试验。已经研究了几种主要用于解决P-gp的药物递送系统,观察到的改善的抗癌功效表明,纳米药物为克服癌症中的MDR提供了新的机会。在这篇综述中,将在低分子量药物和RNAi分子抑制P-gp的背景下讨论结肠癌治疗的新治疗策略。

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