Inhibition of lung tumor growth by complex pulmonary delivery of drugs with oligonucleotides as suppressors of cellular resistance
Inhibition of lung tumor growth by complex pulmonary delivery of drugs with oligonucleotides as suppressors of cellular resistance
复制标题
DOI：
10.1073/pnas.1004604107
复制
发表时间：
2010-06-08
影响因子：
11.1
通讯作者：
Minko, Tamara
中科院分区：
文献类型：
--
作者：
Garbuzenko, Olga B.;Saad, Maha;Minko, Tamara
肿瘤细胞的耐药、治疗药物在肺部的低蓄积以及严重的不良副作用是肺癌有效化疗的主要障碍。为了克服这些困难，我们建议吸入局部给药，联合泵和非泵细胞耐药抑制剂。为了验证这种方法，研究人员开发了基于纳米级的递送系统，该系统含有多柔比星作为细胞死亡诱导剂，针对MRP1 mRNA（泵抗性抑制因子）和BCL2 mRNA（非泵抗性抑制因子）的反义寡核苷酸，并在人肺癌原位小鼠模型上进行了检测。实验结果表明，所提出的复杂吸入治疗具有高的抗肿瘤活性和低的不良副作用，这是单独应用单个成分无法实现的。目前的工作可能有助于肺癌的治疗，通过描述一个独特的组合局部吸入输送药物和抑制泵和非泵细胞耐药。
Development of cancer cell resistance, low accumulation of therapeutic drug in the lungs, and severe adverse treatment side effects represent main obstacles to efficient chemotherapy of lung cancer. To overcome these difficulties, we propose inhalation local delivery of anticancer drugs in combination with suppressors of pump and nonpump cellular resistance. To test this approach, nanoscale-based delivery systems containing doxorubicin as a cell death inducer, antisense oligonucleotides targeted to MRP1 mRNA as a suppressor of pump resistance and to BCL2 mRNA as a suppressor of nonpump resistance, were developed and examined on an orthotopic murine model of human lung carcinoma. The experimental results show high antitumor activity and low adverse side effects of proposed complex inhalatory treatment that cannot be achieved by individual components applied separately. The present work potentially contributes to the treatment of lung cancer by describing a unique combinatorial local inhalation delivery of drugs and suppressors of pump and nonpump cellular resistance.