title: Dual targeting luminescent gold nanoclusters for tumor imaging and deep tissue therapy.
abstract: Dual targeting towards both extracellular and intracellular receptors specific to tumor is a significant approach for cancer diagnosis and therapy. In the present study, a novel nano-platform (AuNC-cRGD-Apt) with dual targeting function was initially established by conjugating gold nanocluster (AuNC) with cyclic RGD (cRGD) that is specific to αvβ3integrins over-expressed on the surface of tumor tissues and aptamer AS1411 (Apt) that is of high affinity to nucleolin over-expressed in the cytoplasm and nucleus of tumor cells. Then, AuNC-cRGD-Apt was further functionalized with near infrared (NIR) fluorescence dye (MPA), giving a NIR fluorescent dual-targeting probe AuNC-MPA-cRGD-Apt. AuNC-MPA-cRGD-Apt displays low cytotoxicity and favorable tumor-targeting capability at both in vitro and in vivo level, suggesting its clinical potential for tumor imaging. Additionally, Doxorubicin (DOX), a widely used clinical chemotherapeutic drug that kill cancer cells by intercalating DNA in cellular nucleus, was immobilized onto AuNC-cRGD-Apt forming a pro-drug, AuNC-DOX-cRGD-Apt. The enhanced tumor affinity, deep tumor penetration and improved anti-tumor activity of this pro-drug were demonstrated in different tumor cell lines, tumor spheroid and tumor-bearing mouse models. Results in this study suggest not only the prospect of non-toxic AuNC modified with two targeting ligands for tumor targeted imaging, but also confirm the promising future of dual targeting AuNC as a core for the design of prodrug in the field of cancer therapy.
authors.affiliation: Department of Biomedical Engineering, School of Engineering, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, USA.
authors.forename: Bowen
authors.initials: B
authors.lastname: Li
authors.affiliation: Nanjing University Sub-Atomic Resolution Electron Microscopy Laboratory, College of Engineering and Applied Sciences, Nanjing University, China.
authors.forename: Songhua
authors.initials: S
authors.lastname: Cai
authors.affiliation: Nanjing University Sub-Atomic Resolution Electron Microscopy Laboratory, College of Engineering and Applied Sciences, Nanjing University, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, School of Engineering, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Biomedical Engineering, School of Engineering, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China.
authors.forename: Yuanzhi
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Department of Biomedical Engineering, School of Engineering, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Biomedical Engineering, School of Engineering, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China. Electronic address: guyueqingsubmission@hotmail.com.
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Biomedical Engineering, School of Engineering, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China. Electronic address: chenhaiyan@cpu.edu.cn.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D052157:Aptamers, Nucleotide; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005260:Female; D006046:Gold / Q000737:chemistry*; D006801:Humans; D049408:Luminescent Agents / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry; D008819:Mice, Nude; D018613:Microscopy, Confocal; D058726:Nanoconjugates / Q000737:chemistry*; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry
chemical_list: C513936:AGRO 100; D000903:Antibiotics, Antineoplastic; D052157:Aptamers, Nucleotide; D049408:Luminescent Agents; D058726:Nanoconjugates; D009838:Oligodeoxyribonucleotides; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; D006046:Gold; D004317:Doxorubicin
keywords: Aptamer; Gold nanoclusters; Tumor diagnosis; Tumor spheroid; Tumor-targeting; Tumor-targeting therapy