Aptamer-Mediated Delivery of Chemotherapy to Pancreatic Cancer Cells
Aptamer-Mediated Delivery of Chemotherapy to Pancreatic Cancer Cells
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DOI：
10.1089/nat.2012.0353
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发表时间：
2012-10-01
影响因子：
4
通讯作者：
White, Rebekah R.
中科院分区：
文献类型：
--
作者：
Ray, Partha;Cheek, Marcus A.;White, Rebekah R.
吉西他滨是一种核苷类似物，是目前治疗胰腺癌的最佳单药化疗药物。然而，由于我们无法将足够的活性代谢物输送到癌细胞中而不对正常组织产生毒性作用，其疗效受到限制。靶向递送吉西他滨到癌细胞可以最大限度地提高疗效，同时减少毒副作用，减少正常细胞的摄取。大多数胰腺癌过表达表皮生长因子受体（EGFR），一种跨膜受体酪氨酸激酶。我们利用一种核酸酶抗性RNA适配体结合并被胰腺癌细胞上的EGFR内化，将含有吉西他滨的聚合物输送到表达EGFR的细胞中，并在体外抑制细胞增殖。这种细胞类型特异性治疗方法可以适用于其他靶点和其他类型的治疗货物。
Gemcitabine is a nucleoside analog that is currently the best available single-agent chemotherapeutic drug for pancreatic cancer. However, efficacy is limited by our inability to deliver sufficient active metabolite into cancer cells without toxic effects on normal tissues. Targeted delivery of gemcitabine into cancer cells could maximize effectiveness and concurrently minimize toxic side effects by reducing uptake into normal cells. Most pancreatic cancers overexpress epidermal growth factor receptor (EGFR), a trans-membrane receptor tyrosine kinase. We utilized a nuclease resistant RNA aptamer that binds and is internalized by EGFR on pancreatic cancer cells to deliver gemcitabine-containing polymers into EGFR-expressing cells and inhibit cell proliferation in vitro. This approach to cell type-specific therapy can be adapted to other targets and to other types of therapeutic cargo.