Quantum dot - Aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on Bi-fluorescence resonance energy transfer

Quantum dot - Aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on Bi-fluorescence resonance energy transfer
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DOI:
10.1021/nl071546n
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发表时间:
2007-10-01
期刊:
影响因子:
10.8
通讯作者:
Farokhzad, Omid C.
Farokhzad, Omid C.
中科院分区:
材料科学1区
文献类型:
--
作者:
Bagalkot, Vaishali;Zhang, Liangfang;Farokhzad, Omid C.

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我们报告了一种新型量子点(QD)-适体(Apt)-阿霉素(Dox)缀合物[QD-Apt(Dox)]作为靶向癌症成像、治疗和传感系统。通过使用 A10 RNA 适体功能化荧光 QD 表面,A10 RNA 适体可识别前列腺特异性膜抗原 (PSMA) 的胞外结构域,我们开发了一种靶向 QD 成像系统 (QD-Apt),能够对表达 PSMA 蛋白的前列腺癌细胞进行差异摄取和成像。 Dox(一种广泛使用的具有荧光特性的抗肿瘤蒽环类药物)嵌入 A10 适配体的双链茎中,产生了基于 Bi-FRET 机制的具有可逆自猝灭特性的靶向 QD-Apt(Dox) 缀合物。当 Dox 嵌入 A10 适体中时,会产生 QD 和 Dox 之间的供体-受体模型荧光共振能量转移 (FRET) 以及 Dox 和适体之间的供体-猝灭剂模型 FRET。这种简单的多功能纳米颗粒系统可以将 Dox 递送至目标前列腺癌细胞,并通过激活 QD 的荧光来感知 Dox 的递送,同时对癌细胞进行成像。我们证明了这种纳米颗粒缀合物作为体外癌症成像、治疗和传感系统的特异性和敏感性。
We report a novel quantum dot (QD)-aptamer(Apt)-doxorubicin (Dox) conjugate [QD-Apt(Dox)] as a targeted cancer imaging, therapy, and sensing system. By functionalizing the surface of fluorescent QD with the A10 RNA aptamer, which recognizes the extracellular domain of the prostate specific membrane antigen (PSMA), we developed a targeted QD imaging system (QD-Apt) that is capable of differential uptake and imaging of prostate cancer cells that express the PSMA protein. The intercalation of Dox, a widely used antineoplastic anthracycline drug with fluorescent properties, in the double-stranded stem of the A10 aptamer results in a targeted QD-Apt(Dox) conjugate with reversible self-quenching properties based on a Bi-FRET mechanism. A donor-acceptor model fluorescence resonance energy transfer (FRET) between QD and Dox and a donor-quencher model FRET between Dox and aptamer result when Dox intercalated within the A10 aptamer. This simple multifunctional nanoparticle system can deliver Dox to the targeted prostate cancer cells and sense the delivery of Dox by activating the fluorescence of QD, which concurrently images the cancer cells. We demonstrate the specificity and sensitivity of this nanoparticle conjugate as a cancer imaging, therapy and sensing system in vitro.