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Cellular Uptake and Intra-Organ Biodistribution of Functionalized Silica-Coated Gold Nanorods

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Abstract

Purpose

To develop a new nanobiosystem based on folate-functionalized silica-coated gold nanorods and to investigate its cellular uptake and intra-organ biodistribution in vitro and in vivo.

Procedures

Ellipsoidal silica-coated gold nanorods (GNRs@SIO2) were prepared by seeded growth method using silicon dioxide (SIO2) as the shell material. Rhodamine-labeled GNRs@SiO2-folic acid (FA) were obtained by reacting the amino group located on GNRs@SiO2-FA with rhodamine isothiocyanate. The characteristics of the prepared GNRs@SiO2-FA were studied using transmission electron microscopy (TEM) and UV spectra. The 3-[4, 5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) colorimetric method was used to assess the biocompatibility of GNRs@SiO2-FA, and their uptake into cells was observed using TEM. In vivo experiments of cellular uptake and study of the intra-organ biodistribution of GNRs@SiO2-FA were detected using intrinsic two-photon luminescence.

Results

Analysis of UV spectra confirmed the successfu1 preparation of GNRs@SiO2-FA. Results of the MTT assay demonstrated that surface modification of GNRs@SiO2-FA resulted in excellent biocompatibility. TEM examination revealed that GNRs@SiO2-FA entered the cells via endocytosis, which could connect to cancer cells with high folic acid expression. We found that GNRs exhibit bright luminescence and could be visualized in vivo by direct imaging of these particles within the tissue. Additionally, GNRs@SiO2-FA could specifically bind to tumor cells. GNRs@SiO2-FA entered tumor cells within 24 h and had a heterogeneous distribution with higher accumulation at the tumor cytoplasm.

Conclusion

GNRs@SiO2-FA can bind to cells and were found to be internalized by targeted folate receptor-expressing cells via a ligand-receptor-mediated endocytosis pathway, which is very useful in diagnosing diseases as well as in treating neoplasm with I-125 particles.

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Acknowledgments

The authors gratefully acknowledge Dr. B. Gao for the insightful discussions and access to the measurement facility and Dr. W. H. Xiao for the helpful discussion. The authors also acknowledge the University of Science and Technology of China and the National Science Foundation grant 81071240 for the financial assistance.

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Authors and Affiliations

  1. Department of Interventional Radiology, Third Affiliated Hospital, Anhui Medical University, Hefei, 230061, Anhui Province, China

    Bin Gao, Jun Xu, ke-wu He, Lei Shen, Hao Chen, Hui-jun Yang & Ai-hua Li

  2. School of Life Science, University of Science and Technology of China, Hefei, 230022, Anhui Province, China

    Wei-hua Xiao

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  1. Bin Gao
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  2. Jun Xu
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  3. ke-wu He
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  4. Lei Shen
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Correspondence to Bin Gao.

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The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

Animal studies were carried out under the supervision of a veterinarian according to the Guidelines of for the Use of Laboratory Animals of the Ministry of Public Health of China. All animals were provided by the Laboratory Animal Center of Anhui Medical University, and all protocols were approved by the Animal Use and Care Committee and Medical Ethics Committee of Anhui Medical University.

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Gao, B., Xu, J., He, kw. et al. Cellular Uptake and Intra-Organ Biodistribution of Functionalized Silica-Coated Gold Nanorods. Mol Imaging Biol 18, 667–676 (2016). https://doi.org/10.1007/s11307-016-0938-9

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