title: Tumor Angiogenesis Targeted Radiosensitization Therapy Using Gold Nanoprobes Guided by MRI/SPECT Imaging.
abstract: Gold nanoparticles (AuNPs) have recently garnered great interest as potential radiosensitizers in tumor therapy. However, major challenges facing their application in this regard are further enhancement of tumor accumulation of the particles in addition to enhanced permeability retention (EPR) effect and an understanding of the optimal particle size and time for applying radiotherapy after the particle administration. In this study, we fabricated novel cyclic c(RGDyC)-peptide-conjugated, Gd- and 99 mTc-labeled AuNPs (RGD@AuNPs-Gd99 mTc) probes with different sizes (29, 51, and 80 nm) and evaluated their potential as radiosensitization therapy both in vitro and in vivo. We found that these probes have a high specificity for αvβ3 integrin positive cells, which resulted in their high cellular uptake and thereby enhanced radiosensitization. Imaging in vivo with MRI and SPECT/CT directly showed that the RGD@AuNPs-Gd99 mTc probes specifically target tumors and exhibit greater accumulation within tumors than the RAD@AuNPs-Gd99 mTc probes. Interestingly, we found that the 80 nm RGD@AuNPs-Gd99 mTc probes exhibit the greatest effects in vitro; however, the 29 nm RGD@AuNPs-Gd99 mTc probes were clearly most efficient in vivo. As a result, radiotherapy of tumors with the 29 nm probe was the most potent. Our study demonstrates that RGD@AuNPs-Gd99 mTc probes are highly useful radiosensitizers capable of guiding and enhancing radiation therapy of tumors.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Biomedical Engineering, Shanghai Jiao Tong University , Shanghai 200030, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Biomedical Engineering, Shanghai Jiao Tong University , Shanghai 200030, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Changzheng Hospital, Secondary Military Medical University , Shanghai 200003, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University , Shanghai 200032, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University , Shanghai 200032, China.
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University , Shanghai 200240, China.
authors.forename: Huilan
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Nuclear Medicine, Shanghai Cancer Center, Fudan University , Shanghai 200032, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Changzheng Hospital, Secondary Military Medical University , Shanghai 200003, China.
authors.forename: Shiyuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University , Shanghai 200032, China.
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Nuclear Medicine, Shanghai Cancer Center, Fudan University , Shanghai 200032, China.
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Biomedical Engineering, Shanghai Jiao Tong University , Shanghai 200030, China.|Department of Nuclear Medicine, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200025, China.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005682:Gadolinium / Q000737:chemistry; D006046:Gold / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3; D008279:Magnetic Resonance Imaging; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000532:radiotherapy; D009389:Neovascularization, Pathologic / Q000628:therapy*; D009842:Oligopeptides / Q000737:chemistry; D011836:Radiation Tolerance; D013347:Subcellular Fractions / Q000378:metabolism; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D013667:Technetium; D006046:Gold; C047981:arginyl-glycyl-aspartic acid; D005682:Gadolinium
keywords: MRI/SPECT; gold nanoparticles; radiotherapy; theranostics; αvβ3 integrin