Saw Phei Er, Park Jinho, Jon Sangyong, Farokhzad Omid C
Department of Anesthesia, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Nanomedicine. 2017 Feb;13(2):713-722. doi: 10.1016/j.nano.2016.10.005. Epub 2016 Oct 19.
A major problem with cancer chemotherapy begins when cells acquire resistance. Drug-resistant cancer cells typically upregulate multi-drug resistance proteins such as P-glycoprotein (P-gp). However, the lack of overexpressed surface biomarkers has limited the targeted therapy of drug-resistant cancers. Here we report a drug-delivery carrier decorated with a targeting ligand for a surface marker protein extra-domain B(EDB) specific to drug-resistant breast cancer cells as a new therapeutic option for the aggressive cancers. We constructed EDB-specific aptide (APT)-conjugated liposome to simultaneously deliver siRNA(siMDR1) and Dox to drug-resistant breast cancer cells. APT-LS(Dox,siMDR1) led to enhanced delivery of payloads into MCF7/ADR cells and showed significantly higher accumulation and retention in the tumors. While either APT-LS(Dox) or APT-LS(siMDR1) did not lead to appreciable tumor retardation in MCF7/ADR orthotropic model, APT-LS(Dox,siMDR1) treatment resulted in significant reduction of the drug-resistant breast tumor. Taken together, this study provides a new strategy of drug delivery for drug-resistant cancer therapy.
癌症化疗的一个主要问题始于细胞产生耐药性。耐药癌细胞通常会上调多药耐药蛋白，如P-糖蛋白（P-gp）。然而，缺乏过表达的表面生物标志物限制了耐药癌症的靶向治疗。在此，我们报道了一种载药载体，其装饰有针对耐药乳腺癌细胞特异性表面标志物蛋白额外结构域B（EDB）的靶向配体，作为侵袭性癌症的一种新治疗选择。我们构建了EDB特异性适配体（APT）偶联脂质体，以同时将小干扰RNA（siMDR1）和阿霉素递送至耐药乳腺癌细胞。APT-LS（Dox，siMDR1）使有效载荷增强递送至MCF7/ADR细胞，并在肿瘤中显示出显著更高的积累和滞留。虽然APT-LS（Dox）或APT-LS（siMDR1）在MCF7/ADR原位模型中均未导致明显的肿瘤生长迟缓，但APT-LS（Dox，siMDR1）治疗导致耐药性乳腺肿瘤显著缩小。综上所述，本研究为耐药癌症治疗提供了一种新的药物递送策略。
