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DNA Origami-Enabled Engineering of Ligand-Drug Conjugates for Targeted Drug Delivery.
Small ( IF 13.0 ) Pub Date : 2020-03-19 , DOI: 10.1002/smll.201904857 Zhilei Ge 1 , Linjie Guo 2 , Guangqi Wu 3 , Jiang Li 2 , Yunlong Sun 3 , Yingqin Hou 3 , Jiye Shi 2 , Shiping Song 2 , Lihua Wang 2 , Chunhai Fan 1 , Hua Lu 3 , Qian Li 1
Small ( IF 13.0 ) Pub Date : 2020-03-19 , DOI: 10.1002/smll.201904857 Zhilei Ge 1 , Linjie Guo 2 , Guangqi Wu 3 , Jiang Li 2 , Yunlong Sun 3 , Yingqin Hou 3 , Jiye Shi 2 , Shiping Song 2 , Lihua Wang 2 , Chunhai Fan 1 , Hua Lu 3 , Qian Li 1
Affiliation
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Effective drug delivery systems that can systematically and selectively transport payloads to disease cells remain a challenge. Here, a targeting ligand-modified DNA origami nanostructure (DON) as an antibody-drug conjugate (ADC)-like carrier for targeted prostate cancer therapy is reported. Specifically, DON of six helical bundles is modified with a ligand 2-[3-(1,3-dicarboxy propyl)-ureido] pentanedioic acid (DUPA) against prostate-specific membrane antigen (PSMA), to serve as the antibody for drug conjugation in ADC. Doxorubicin (Dox) is then loaded to DON through intercalation to dsDNA. This platform features in spatially controllable organization of targeting ligands and high drug loading capacity. With this nanocomposite, selective delivery of Dox to the PSMA+ cancer cell line LNCaP is readily achieved. The consequent therapeutic efficacy is critically dependent on the numbers of targeting ligand assembled on DON. This target-specific and biocompatible drug delivery platform with high maximum tolerated doses shows immense potential for developing novel nanomedicine.
中文翻译：
基于DNA折纸的配体-药物偶联物工程技术可用于靶向药物递送。
能够将有效载荷系统地和选择性地转移到疾病细胞的有效药物递送系统仍然是一个挑战。在此，报道了靶向配体修饰的DNA折纸纳米结构（DON）作为用于靶向前列腺癌治疗的抗体-药物缀合物（ADC）样载体。具体来说，用针对前列腺特异性膜抗原（PSMA）的配体2- [3-（1,3-二羧基丙基）-脲基]戊二酸（DUPA）修饰六个螺旋束的DON，以用作药物抗体ADC中的共轭。然后通过插入dsDNA将阿霉素（Dox）加载到DON。该平台的特征在于靶向配体的空间可控组织和高载药量。使用这种纳米复合材料，很容易实现将Dox选择性递送至PSMA +癌细胞系LNCaP。随之而来的治疗功效至关重要地取决于在DON上组装的靶向配体的数量。具有最高最大耐受剂量的这种靶标特异性且生物相容的药物递送平台显示出开发新型纳米药物的巨大潜力。
更新日期：2020-04-22
中文翻译：
基于DNA折纸的配体-药物偶联物工程技术可用于靶向药物递送。
能够将有效载荷系统地和选择性地转移到疾病细胞的有效药物递送系统仍然是一个挑战。在此，报道了靶向配体修饰的DNA折纸纳米结构（DON）作为用于靶向前列腺癌治疗的抗体-药物缀合物（ADC）样载体。具体来说，用针对前列腺特异性膜抗原（PSMA）的配体2- [3-（1,3-二羧基丙基）-脲基]戊二酸（DUPA）修饰六个螺旋束的DON，以用作药物抗体ADC中的共轭。然后通过插入dsDNA将阿霉素（Dox）加载到DON。该平台的特征在于靶向配体的空间可控组织和高载药量。使用这种纳米复合材料，很容易实现将Dox选择性递送至PSMA +癌细胞系LNCaP。随之而来的治疗功效至关重要地取决于在DON上组装的靶向配体的数量。具有最高最大耐受剂量的这种靶标特异性且生物相容的药物递送平台显示出开发新型纳米药物的巨大潜力。
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