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用于癌症诊疗中靶向前药递送的银纳米簇嵌入复合纳米颗粒

Silver Nanocluster Embedded Composite Nanoparticles for Targeted Prodrug Delivery in Cancer Theranostics.

作者信息

Sahoo Amaresh Kumar, Goswami Upashi, Dutta Deepanjalee, Banerjee Subhamoy, Chattopadhyay Arun, Ghosh Siddhartha Sankar

机构信息

Centre for Nanotechnology, ‡Department of Biosciences and Bioengineering, and §Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, Assam, India.

Centre for Nanotechnology, Department of Biosciences and Bioengineering, and §Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, Assam, India.

出版信息

ACS Biomater Sci Eng. 2016 Aug 8;2(8):1395-1402. doi: 10.1021/acsbiomaterials.6b00334. Epub 2016 Jul 8.

Abstract

Cancer therapy with theranostic nanoparticles having the dual properties of concurrent delivery of therapeutics and its tracking offers a huge prospect to overcome the limitations of conventional therapy. Delivery of the nontoxic prodrug, which converts into the toxic drug due to cellular stimuli, offers a great deal of scope in cancer therapy. The paracetamol dimer (PD) generally considered as nontoxic is encapsulated with fluorescent silver nanocluster (Ag NC) embedded composite nanoparticles where it acts as a prodrug. This is possibly converted to a toxic metabolite due to elevated reactive oxygen species (ROS), leading to apoptosis mediated cell death. Conjugation of folic acid with these composite NPs offers the credibility of distinguishing between two different cancer cell lines such as HeLa, which overexpresses folic acid receptors, and A549, which down-regulates its expression, probed by the fluorescence intensity of Ag NCs. Importantly, Ag NCs along with PD synergistically induce prodrug mediated targeted cell death at a much reduced concentration of silver. Thus, theranostic nanocarriers have been developed offering the dual property of therapy and imaging based on the differential uptake.

摘要

具有治疗药物同步递送及其追踪双重特性的治疗诊断纳米颗粒用于癌症治疗,为克服传统治疗的局限性提供了巨大前景。无毒前药的递送因细胞刺激而转化为有毒药物,在癌症治疗中具有很大的应用范围。通常被认为无毒的对乙酰氨基酚二聚体(PD)被包裹在嵌入荧光银纳米簇(Ag NC)的复合纳米颗粒中,在此它作为前药。由于活性氧(ROS)水平升高,其可能转化为有毒代谢物,导致凋亡介导的细胞死亡。叶酸与这些复合纳米颗粒的缀合提供了区分两种不同癌细胞系的能力,如过表达叶酸受体的HeLa细胞系和下调其表达的A549细胞系,这通过Ag NCs的荧光强度来探测。重要的是,Ag NCs与PD协同作用,在银浓度大大降低的情况下诱导前药介导的靶向细胞死亡。因此,基于差异摄取开发了具有治疗和成像双重特性的治疗诊断纳米载体。

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