Paramagnetic hollow silica nanospheres for in vivo targeted ultrasound and magnetic resonance imaging

Lu An; He Hu; Jing Du; Jie Wei; Li Wang; Hong Yang; Dongmei Wu; Haili Shi; Fenghua Li; Shiping Yang

doi:10.1016/j.biomaterials.2014.03.030

Paramagnetic hollow silica nanospheres for in vivo targeted ultrasound and magnetic resonance imaging

Biomaterials. 2014 Jul;35(20):5381-5392. doi: 10.1016/j.biomaterials.2014.03.030. Epub 2014 Apr 3.

Authors

Lu An¹, He Hu², Jing Du³, Jie Wei¹, Li Wang¹, Hong Yang¹, Dongmei Wu⁴, Haili Shi¹, Fenghua Li³, Shiping Yang⁵

Affiliations

¹ The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, PR China.
² The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, PR China. Electronic address: huheandy@shnu.edu.cn.
³ Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, PR China.
⁴ Shanghai Key Laboratory of Magnetic Resonance, Department of Physics, East China Normal University, Shanghai 200062, PR China.
⁵ The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, PR China. Electronic address: shipingy@shnu.edu.cn.

PMID: 24703718
DOI: 10.1016/j.biomaterials.2014.03.030

Abstract

A series of hollow silica nanospheres (HSNSs) with sizes ranging from 100 to 400 nm were synthesized and used for primary ultrasound imaging (US) efficiency assessment. The 400 nm HSNSs were chosen as platform for conjugation with Gd-DTPA and cyclo-arginine-glycine-aspartic acid c(RGD) peptide to construct US and magnetic resonance imaging (MRI) dual-modal contrast agents (CAs): [HSNSs@(DTPA-Gd)-RGD]. The obtained CAs displayed good physiological stability, low cytotoxicity and negligible hemolytic activity in vitro. Furthermore, the passive accumulation and active-targeting of the HSNSs in the tumor site of mice was demonstrated by US and MR imaging, respectively. The qualitative and quantitative biodistribution of the HSNSs showed that they mainly accumulated in the tissues of liver, lung, tumor after intravenous administration and then be excreted from feces. In addition, histological, hematological, blood and biochemical analysis were used to further study toxicity of the HSNSs, and all results indicated that there were no covert toxicity of HSNSs in mice after long exposure times. Findings from this study indicated that the silica-based paramagnetic HSNSs can be used as a platform for long-term targeted imaging and therapy studies safely in vivo.

Keywords: Biodistribution; Hollow silica nanospheres; Magnetic resonance imaging; Toxicity; Ultrasound imaging.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Intravenous
Animals
Cell Line, Tumor
Contrast Media
Disease Models, Animal
Drug Delivery Systems
Feces / chemistry
Gadolinium DTPA / chemistry
Gadolinium DTPA / pharmacokinetics
Humans
Liver / metabolism
Lung / metabolism
Magnetic Resonance Imaging / methods*
Male
Mice
Mice, Nude
Nanospheres / chemistry*
Neoplasm Transplantation
Neoplasms / diagnostic imaging*
Oligopeptides / chemistry
Oligopeptides / pharmacokinetics
Polystyrenes / chemistry
Silicon Dioxide / chemistry*
Silicon Dioxide / pharmacokinetics
Tissue Distribution
Ultrasonography

Substances

Contrast Media
Oligopeptides
Polystyrenes
Silicon Dioxide
arginyl-glycyl-aspartic acid
Gadolinium DTPA