title: Dendrimer-entrapped gold nanoparticles modified with RGD peptide and alpha-tocopheryl succinate enable targeted theranostics of cancer cells.
abstract: We report here the synthesis of multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) modified with alpha-tocopheryl succinate (α-TOS) and arginine-glycine-aspartic acid (RGD) peptide for targeted chemotherapy and computed tomography (CT) imaging of cancer cells. In this work, generation 5 poly(amidoamine) dendrimers pre-conjugated with fluorescein isothiocyanate (FI), RGD peptide via a polyethylene glycol (PEG) spacer, and PEG-linked α-TOS were used as templates to synthesize AuNPs. Followed by acetylation of the remaining dendrimer terminal amines, multifunctional Au DENPs with an Au core size of 4.0nm were generated. The formed multifunctional Au DENPs were characterized via different techniques. We show that the multifunctional Au DENPs are stable at different pH (5-8) and temperature (4-50°C) conditions and display enhanced efficacy in the generation of reactive oxygen species, which is associated with their increased ability to induce apoptosis. Thanks to the role played by RGD-mediated targeting, the multifunctional Au DENPs are able to target cancer cells overexpressing αvβ3 integrin and specifically inhibit the growth of the cancer cells. Likewise, the existence of AuNPs enabled the multifunctional Au DENPs to have a better X-ray attenuation property than clinically used iodinated CT contrast agents (e.g., Omnipaque) and the use of them as a nanoprobe for targeted CT imaging of cancer cells in vitro. The formed multifunctional Au DENPs may hold great promise to be used as a theranostic platform for cancer theranostics.
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Zhu
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Fanfan
authors.initials: F
authors.lastname: Fu
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Zhijuan
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China.
authors.forename: Mingwu
authors.initials: M
authors.lastname: Shen
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, People's Republic of China; College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, People's Republic of China. Electronic address: xshi@dhu.edu.cn.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
mesh_terms: D050091:Dendrimers; D006046:Gold / Q000737:chemistry*; D053768:Metal Nanoparticles; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D009842:Oligopeptides / Q000008:administration & dosage*; D000068936:Theranostic Nanomedicine; D014057:Tomography, X-Ray Computed; D024502:alpha-Tocopherol / Q000008:administration & dosage*
chemical_list: D050091:Dendrimers; D009842:Oligopeptides; D006046:Gold; C047981:arginyl-glycyl-aspartic acid; D024502:alpha-Tocopherol
keywords: Alpha-tocopheryl succinate; Dendrimers; Gold nanoparticles; RGD peptide; Theranostics