title: pH-Dependent Transmembrane Activity of Peptide-Functionalized Gold Nanostars for Computed Tomography/Photoacoustic Imaging and Photothermal Therapy.
abstract: Progress in multifunctional nanomaterials for tumor therapy mostly depends on the development of tumor-targeting delivery strategies. One approach is to explore a pH-responsive strategy to target the slightly acidic solid tumor microenvironment. A novel class of pH (low) insertion peptides (pHLIPs) with pH-dependent transmembrane activity can fold and rapidly insert into the lipid bilayer of tumor cells triggered by acidity, facilitating the cellular internalization of nanomaterials synchronously. Here, we innovatively decorated gold nanostars (GNSs) with pHLIPs (GNS-pHLIP) to improve their targeting ability and photothermal therapeutic (PTT) efficiency. The obtained GNS-pHLIP exhibited the excellent characteristics of uniform size and good biocompatibility. As compared to GNS-mPEG, the cellular internalization of GNS-pHLIP was 1-fold higher after a 2 h incubation with cells in media at pH 6.4 than at pH 7.4. Moreover, the tumor accumulation of the GNS-pHLIP was 3-fold higher than that of GNS-mPEG after intravenous injection into MCF-7 breast tumor animal models for 24 h. Furthermore, GNS-pHLIP exhibited stronger signals than the GNS-mPEG through computed tomography (CT) and photoacoustic (PA) imaging. Simultaneously, the desirable targeting efficiency significantly improved the PTT efficacy to tumors, with low side effects on normal tissues. The results clearly demonstrate that the GNS-pHLIP successfully took advantage of the tumor-targeting ability of pHLIPs and the good characteristics of GNSs, which may contribute to the study of tumor imaging and therapy.
authors.affiliation: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, People's Republic of China.
authors.forename: Yunlei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, People's Republic of China.|State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, People's Republic of China.
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Teng
authors.affiliation: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Kong
authors.affiliation: Key Laboratory for Organic Electronics & Information Displays and Institute of Advanced Materials, Nanjing University of Posts and Telecommunications , Nanjing 210046, People's Republic of China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, People's Republic of China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, People's Republic of China.
authors.forename: Shouju
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing 210002, People's Republic of China.|State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210093, People's Republic of China.
authors.forename: Guangming
authors.identifier: http://orcid.org/0000-0003-4913-2314
authors.initials: G
authors.lastname: Lu
mesh_terms: D000818:Animals; D002462:Cell Membrane; D016503:Drug Delivery Systems; D006046:Gold; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D049329:Nanostructures; D010455:Peptides; D061088:Photoacoustic Techniques
chemical_list: D010455:Peptides; D006046:Gold
keywords: computed tomography; gold nanostars; pH (low) insertion peptides; pH-responsive strategy; photoacoustic imaging; photothermal therapy