Darvishi Behrad, Farahmand Leila, Majidzadeh-A Keivan
Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, 1517964311 Tehran, Iran.
Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, 1517964311 Tehran, Iran.
Mol Ther Nucleic Acids. 2017 Jun 16;7:164-180. doi: 10.1016/j.omtn.2017.03.007. Epub 2017 Mar 29.
Triple negative breast cancer (TNBC) is the most aggressive and lethal subtype of breast cancer. It is associated with a very poor prognosis and intrinsically resistant to several conventional and targeted chemotherapy agents and has a 5-year survival rate of less than 25%. Because the treatment options for TNBC are very limited and not efficient enough for achieving minimum desired goals, shifting toward a new generation of anti-cancer agents appears to be very critical. Among recent alternative approaches being proposed, small interfering RNA (siRNA) gene therapy can potently suppress Bcl-2 proto-oncogene and p-glycoprotein gene expression, the most important chemotherapy resistance inducers in TNBC. When resensitized, primarily ineffective chemotherapy drugs turn back into valuable sources for further intensive chemotherapy. Regrettably, siRNA's poor stability, rapid clearance in the circulatory system, and poor cellular uptake mostly hampers the beneficial outcomes of siRNA therapy. Considering these drawbacks, dual siRNA/chemotherapy drug encapsulation in targeted delivery vehicles, especially mesoporous silica nanoparticles (MSNs) appears to be the most reasonable solution. The literature is full of reports of successful treatments of multi-drug-resistant cancer cells by administration of dual drug/siRNA-loaded MSNs. Here we tried to answer the question of whether application of a similar approach with identical delivery devices in TNBC is rational.
三阴性乳腺癌（TNBC）是乳腺癌中最具侵袭性和致死性的亚型。它与非常差的预后相关，并且对几种传统和靶向化疗药物具有内在抗性，5年生存率低于25%。由于TNBC的治疗选择非常有限且不足以实现最低期望目标，转向新一代抗癌药物似乎至关重要。在最近提出的替代方法中，小干扰RNA（siRNA）基因疗法可以有效抑制Bcl-2原癌基因和P-糖蛋白基因表达，这是TNBC中最重要的化疗抗性诱导因子。当重新致敏时，原本无效的化疗药物会变回进一步强化化疗的宝贵资源。遗憾的是，siRNA的稳定性差、在循环系统中快速清除以及细胞摄取不良大多阻碍了siRNA疗法的有益效果。考虑到这些缺点，将双siRNA/化疗药物封装在靶向递送载体中，尤其是介孔二氧化硅纳米颗粒（MSN）似乎是最合理的解决方案。文献中充满了通过施用负载双药/siRNA的MSN成功治疗多药耐药癌细胞的报道。在这里，我们试图回答在TNBC中应用类似方法并使用相同递送装置是否合理的问题。
