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Transferrin–Copper Nanocluster–Doxorubicin Nanoparticles as Targeted Theranostic Cancer Nanodrug
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2018-01-17 00:00:00 , DOI: 10.1021/acsami.7b15165 Upashi Goswami , Anushree Dutta , Asif Raza , Raghuram Kandimalla 1 , Sanjeeb Kalita 1 , Siddhartha Sankar Ghosh , Arun Chattopadhyay
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2018-01-17 00:00:00 , DOI: 10.1021/acsami.7b15165 Upashi Goswami , Anushree Dutta , Asif Raza , Raghuram Kandimalla 1 , Sanjeeb Kalita 1 , Siddhartha Sankar Ghosh , Arun Chattopadhyay
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Transferrin (Tf)-templated luminescent blue copper nanoclusters (Tf-Cu NCs) are synthesized. They are further formulated into spherical Tf-Cu NC–doxorubicin nanoparticles (Tf-Cu NC–Dox NPs) based on electrostatic interaction with doxorubicin (Dox). The as-synthesized Tf-Cu NC–Dox NPs are explored for bioimaging and targeted drug delivery to delineate high therapeutic efficacy. Förster resonance energy transfer (FRET) within the Tf-Cu NC–Dox NPs exhibited striking red luminescence, wherein the blue luminescence of Tf-Cu NCs (donor) is quenched due to absorption by Dox (acceptor). Interestingly, blue luminescence of Tf-Cu NCs is restored in the cytoplasm of cancer cells upon internalization of the NPs through overexpressed transferrin receptor (TfR) present on the cell surface. Finally, gradual release of Dox from the NPs leads to the generation of its red luminescence inside the nucleus. The biocompatible Tf-Cu NC–Dox NPs displayed superior targeting efficiency on TfR overexpressed cells (HeLa and MCF-7) as compared to the cells expressing less TfR (HEK-293 and 3T3-L1). Combination index (CI) revealed synergistic activity of Tf-Cu NCs and Dox in Tf-Cu NC–Dox NPs. In vivo assessment of the NPs on TfR positive Daltons lymphoma ascites (DLA) bearing mice revealed significant inhibition of tumor growth rendering prolonged survival of the mice.
中文翻译：
转铁蛋白-铜纳米簇-阿霉素纳米颗粒作为靶向治疗肿瘤的纳米药物
合成了转铁蛋白（Tf）模板的发光蓝铜纳米团簇（Tf-Cu NCs）。基于与阿霉素（Dox）的静电相互作用，将它们进一步配制成球形Tf-Cu NC-阿霉素纳米颗粒（Tf-Cu NC-Dox NPs）。研究了合成的Tf-Cu NC-Dox NPs的生物成像和靶向药物递送，以描绘出高疗效。Tf-Cu NC-Dox NP中的Förster共振能量转移（FRET）表现出惊人的红色发光，其中Tf-Cu NCs（供体）的蓝色发光由于Dox（受体）的吸收而被淬灭。有趣的是，当NP通过细胞表面上过表达的转铁蛋白受体（TfR）内化后，Tf-Cu NCs的蓝色发光在癌细胞的细胞质中得以恢复。最后，Dox从NP逐渐释放导致其在核内产生红色发光。与表达较少TfR的细胞（HEK-293和3T3-L1）相比，具有生物相容性的Tf-Cu NC-Dox NP对TfR过表达的细胞（HeLa和MCF-7）显示出优异的靶向效率。组合指数（CI）揭示了Tf-Cu NC-Dox NP中Tf-Cu NCs和Dox的协同活性。在携带TfR阳性道尔顿淋巴瘤腹水（DLA）的小鼠上进行的NP的体内评估显示，肿瘤生长受到显着抑制，从而延长了小鼠的存活时间。
更新日期：2018-01-17
中文翻译：
转铁蛋白-铜纳米簇-阿霉素纳米颗粒作为靶向治疗肿瘤的纳米药物
合成了转铁蛋白（Tf）模板的发光蓝铜纳米团簇（Tf-Cu NCs）。基于与阿霉素（Dox）的静电相互作用，将它们进一步配制成球形Tf-Cu NC-阿霉素纳米颗粒（Tf-Cu NC-Dox NPs）。研究了合成的Tf-Cu NC-Dox NPs的生物成像和靶向药物递送，以描绘出高疗效。Tf-Cu NC-Dox NP中的Förster共振能量转移（FRET）表现出惊人的红色发光，其中Tf-Cu NCs（供体）的蓝色发光由于Dox（受体）的吸收而被淬灭。有趣的是，当NP通过细胞表面上过表达的转铁蛋白受体（TfR）内化后，Tf-Cu NCs的蓝色发光在癌细胞的细胞质中得以恢复。最后，Dox从NP逐渐释放导致其在核内产生红色发光。与表达较少TfR的细胞（HEK-293和3T3-L1）相比，具有生物相容性的Tf-Cu NC-Dox NP对TfR过表达的细胞（HeLa和MCF-7）显示出优异的靶向效率。组合指数（CI）揭示了Tf-Cu NC-Dox NP中Tf-Cu NCs和Dox的协同活性。在携带TfR阳性道尔顿淋巴瘤腹水（DLA）的小鼠上进行的NP的体内评估显示，肿瘤生长受到显着抑制，从而延长了小鼠的存活时间。
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