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Bilayered near-infrared fluorescent nanoparticles based on low molecular weight PEI for tumor-targeted in vivo imaging

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Abstract

To improve the tumor fluorescent imaging results in vivo, bilayered nanoparticles encapsulating a lipophilic near-infrared (NIR) fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotri-carbocyanine iodide (DiR) were prepared using low molecular weight stearic acid-grafted polyethyleneimine and hyaluronic acid (DiR-PgSHA nanoparticles), which were investigated as a novel NIR fluorescent nano-probe for in vivo tumor-targeted optical imaging. These nanoparticles were characterized by transmission electron microscopy (TEM), infrared (IR) spectra, UV-visual absorption, and fluorescent emission spectra. Their cytotoxicity in vitro and hepatotoxicity in vivo were tested by MTT assay and histological study, respectively. In vivo NIR fluorescence imaging of the DiR-PgSHA nanoparticles was performed using a Carestream imaging system. The DiR-PgSHA nanoparticles were sphere shaped with a diameter of approximately 50 nm according to the TEM images. The DiR-PgSHA nanoparticles had a low cytotoxicity in vitro according to the MTT assay and low hepatotoxicity in vivo as determined in histological studies. The fluorescent emission of DiR-PgSHA nanoparticles was stable in pH values of 5–9 in solution, with only slight blue-shifts of the emission maxima at the basic pH range. The DiR-PgSHA nanoparticles exhibited a substantial tumor-targeting ability in the optical imaging with the use of tumor-bearing mice. These results demonstrated that the DiR-PgSHA nanoparticle is an excellent biocompatible nano-probe for in vivo tumor-targeted NIR fluorescence imaging with a potential for clinical applications.

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References

  • Banerji S, Wright AJ, Noble M, Mahoney DJ, Campbell ID, Day AJ, Jackson DG (2007) Structures of the Cd44-hyaluronan complex provide insight into a fundamental carbohydrate-protein interaction. Nat Struct Mol Biol 14:234–239. doi:10.1038/nsmb1201

    Article  Google Scholar 

  • Barar J, Omidi Y (2013) Dysregulated pH in tumor microenvironment checkmates cancer therapy. Bioimpacts 3:149–162. doi:10.5681/bi.2013.036

    Google Scholar 

  • Belguise-Valladier P, Behr JP (2001) Nonviral gene delivery: towards artificial viruses. Cytotechnology 35:197–201. doi:10.1023/A:1013133605406

    Article  Google Scholar 

  • Beyerle A, Irmler M, Beckers J, Kissel T, Stoeger T (2010) Toxicity pathway focused gene expression profiling of PEI-based polymers for pulmonary applications. Mol Pharm 7:727–737. doi:10.1021/mp900278x

    Article  Google Scholar 

  • Brunot C, Ponsonnet L, Lagneau C, Farge P, Picart C, Grosgogeat B (2007) Cytotoxicity of polyethyleneimine (PEI), precursor base layer of polyelectrolyte multilayer films. Biomaterials 28:632–640. doi:10.1016/j.biomaterials.2006.09.026

    Article  Google Scholar 

  • Chen Y, Li X (2011) Near-infrared fluorescent nanocapsules with reversible response to thermal/pH modulation for optical imaging. Biomacromolecules 12:4367–4372. doi:10.1021/bm201350d

    Article  Google Scholar 

  • Choi KY et al (2011) PEGylation of hyaluronic acid nanoparticles improves tumor targetability in vivo. Biomaterials 32:1880–1889. doi:10.1016/j.biomaterials.2010.11.010

    Article  Google Scholar 

  • Dai Z, Gjetting T, Mattebjerg MA, Wu C, Andresen TL (2011) Elucidating the interplay between DNA-condensing and free polycations in gene transfection through a mechanistic study of linear and branched PEI. Biomaterials 32:8626–8634. doi:10.1016/j.biomaterials.2011.07.044

    Article  Google Scholar 

  • Deliolanis NC et al (2014) Deep-Tissue Reporter-Gene Imaging with Fluorescence and Optoacoustic Tomography: a Performance Overview. Mol Imaging Biol. doi:10.1007/s11307-014-0728-1

    Google Scholar 

  • Ghosh SC, Neslihan Alpay S, Klostergaard J (2012) CD44: a validated target for improved delivery of cancer therapeutics. Expert Opin Ther Targets 16:635–650. doi:10.1517/14728222.2012.687374

    Article  Google Scholar 

  • Godovikova TS et al (2013) Ligand-directed acid-sensitive amidophosphate 5-trifluoromethyl-2′-deoxyuridine conjugate as a potential theranostic agent. Bioconjug Chem 24:780–795. doi:10.1021/bc3006072

    Article  Google Scholar 

  • Gong H, Kovar J, Little G, Chen H, Olive DM (2010) In vivo imaging of xenograft tumors using an epidermal growth factor receptor-specific affibody molecule labeled with a near-infrared fluorophore. Neoplasia 12:139–149

    Google Scholar 

  • Hajdu I, Bodnar M, Trencsenyi G, Marian T, Vamosi G, Kollar J, Borbely J (2013) Cancer cell targeting and imaging with biopolymer-based nanodevices. Int J Pharm 441:234–241. doi:10.1016/j.ijpharm.2012.11.038

    Article  Google Scholar 

  • Han J, Burgess K (2010) Fluorescent indicators for intracellular pH. Chem Rev 110:2709–2728. doi:10.1021/cr900249z

    Article  Google Scholar 

  • Hao E, Meng T, Zhang M, Pang W, Zhou Y, Jiao L (2011) Solvent dependent fluorescent properties of a 1,2,3-triazole linked 8-hydroxyquinoline chemosensor: tunable detection from zinc(II) to iron(III) in the CH3CN/H2O system. J Phys Chem A 115:8234–8241. doi:10.1021/jp202700s

    Article  Google Scholar 

  • Harris EN, Baggenstoss BA, Weigel PH (2009) Rat and human HARE/stabilin-2 are clearance receptors for high- and low-molecular-weight heparins. Am J Physiol Gastrointest Liver Physiol 296:G1191–G1199. doi:10.1152/ajpgi.90717.2008

    Article  Google Scholar 

  • He X, Li J, An S, Jiang C (2013) pH-sensitive drug-delivery systems for tumor targeting. Ther Deliv 4:1499–1510. doi:10.4155/tde.13.120

    Article  Google Scholar 

  • Hobel S, Aigner A (2010) Polyethylenimine (PEI)/siRNA-mediated gene knockdown in vitro and in vivo. Methods Mol Biol 623:283–297. doi:10.1007/978-1-60761-588-0_18

    Article  Google Scholar 

  • Jeong JH, Kim SH, Kim SW, Park TG (2005) Polyelectrolyte complex micelles composed of c-raf antisense oligodeoxynucleotide-poly (ethylene glycol) conjugate and poly (ethylenimine): effect of systemic administration on tumor growth. Bioconjug Chem 16:1034–1037. doi:10.1021/bc0497315

    Article  Google Scholar 

  • Justus CR, Dong L, Yang LV (2013) Acidic tumor microenvironment and pH-sensing G protein-coupled receptors. Front Physiol 4:354. doi:10.3389/fphys.2013.00354

    Article  Google Scholar 

  • Kalchenko V et al (2006) Use of lipophilic near-infrared dye in whole-body optical imaging of hematopoietic cell homing. J Biomed Opt 11:050507. doi:10.1117/1.2364903

    Article  Google Scholar 

  • Lakowicz JR (1999) Introduction to fluorescence. Principles of fluorescence spectroscopy. Springer, New York, pp 1–23

    Chapter  Google Scholar 

  • Lee MJ et al (2010) Rapid pharmacokinetic and biodistribution studies using cholorotoxin-conjugated iron oxide nanoparticles: a novel non-radioactive method. PLoS One 5:e9536. doi:10.1371/journal.pone.0009536

    Article  Google Scholar 

  • Lian W et al (2004) Ultrasensitive detection of biomolecules with fluorescent dye-doped nanoparticles. Anal Biochem 334:135–144. doi:10.1016/j.ab.2004.08.005

    Article  Google Scholar 

  • Liu G et al (2013) Transferrin-modified Doxorubicin-loaded biodegradable nanoparticles exhibit enhanced efficacy in treating brain glioma-bearing rats. Cancer Biother Radiopharm 28:691–696. doi:10.1089/cbr.2013.1480

    Article  Google Scholar 

  • Lu J et al (2013) PEG-derivatized embelin as a nanomicellar carrier for delivery of paclitaxel to breast and prostate cancers. Biomaterials 34:1591–1600. doi:10.1016/j.biomaterials.2012.10.073

    Article  Google Scholar 

  • Necas J, Bartosikova L, Brauner P, Kolar J (2008) Hyaluronic acid (hyaluronan): a review. Vet Med-Czech 53:397–411

    Google Scholar 

  • Nolting DD, Gore JC, Pham W (2011) Near-Infrared DYES: probe development and applications in optical molecular imaging. Curr Org Synth 8:521–534. doi:10.2174/157017911796117223

    Article  Google Scholar 

  • Oliveira S et al (2012) A novel method to quantify IRDye800CW fluorescent antibody probes ex vivo in tissue distribution studies. EJNMMI Res 2:50. doi:10.1186/2191-219X-2-50

    Article  Google Scholar 

  • Pandey MS, Harris EN, Weigel JA, Weigel PH (2008) The cytoplasmic domain of the hyaluronan receptor for endocytosis (HARE) contains multiple endocytic motifs targeting coated pit-mediated internalization. J Biol Chem 283:21453–21461. doi:10.1074/jbc.M800886200

    Article  Google Scholar 

  • Platt VM, Szoka FC Jr (2008) Anticancer therapeutics: targeting macromolecules and nanocarriers to hyaluronan or CD44, a hyaluronan receptor. Mol Pharm 5:474–486. doi:10.1021/mp800024g

    Article  Google Scholar 

  • Schaafsma BE et al (2011) The clinical use of indocyanine green as a near-infrared fluorescent contrast agent for image-guided oncologic surgery. J Surg Oncol 104:323–332. doi:10.1002/jso.21943

    Article  Google Scholar 

  • Schadlich A et al (2011) Tumor accumulation of NIR fluorescent PEG-PLA nanoparticles: impact of particle size and human xenograft tumor model. ACS Nano 5:8710–8720. doi:10.1021/nn2026353

    Article  Google Scholar 

  • Shen J et al (2011) Poly(ethylene glycol)-block-poly(D, L-lactide acid) micelles anchored with angiopep-2 for brain-targeting delivery. J Drug Target 19:197–203. doi:10.3109/1061186X.2010.483517

    Article  Google Scholar 

  • Surace C et al (2009) Lipoplexes targeting the CD44 hyaluronic acid receptor for efficient transfection of breast cancer cells. Mol Pharm 6:1062–1073. doi:10.1021/mp800215d

    Article  Google Scholar 

  • Weiler M, Kassis T, Dixon JB (2012) Sensitivity analysis of near-infrared functional lymphatic imaging. J Biomed Opt 17:066019. doi:10.1117/1.JBO.17.6.066019

    Article  Google Scholar 

  • Yao J, Zhang L, Zhou J, Liu H, Zhang Q (2013) Efficient simultaneous tumor targeting delivery of all-trans retinoid acid and Paclitaxel based on hyaluronic acid-based multifunctional nanocarrier. Mol Pharm 10:1080–1091. doi:10.1021/mp3005808

    Article  Google Scholar 

  • Yoo H, Moon SK, Hwang T, Kim YS, Kim JH, Choi SW, Kim JH (2013) Multifunctional magnetic nanoparticles modified with polyethylenimine and folic acid for biomedical theranostics. Langmuir 29:5962–5967. doi:10.1021/la3051302

    Article  Google Scholar 

  • Yue Y et al (2011) Revisit complexation between DNA and polyethylenimine–effect of length of free polycationic chains on gene transfection. J Control Release 152:143–151. doi:10.1016/j.jconrel.2011.03.020

    Article  Google Scholar 

Download references

Acknowledgments

This study was supported by National Basic Research Program 973 of China (No. 2010CB732603 and No. 2011CB707903), the National Nature Science Foundation of China (Nos. 81271686 and 81228011), the grants of Shaanxi province science and technology and innovation project (Nos. 2011KTCL03-07), US National Institutes of Health Grant (R01 CA121830 S1), K-INBRE (P20 GM103418), and Kansas Bioscience Authority Rising Star Award (to L. X.).

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Authors and Affiliations

  1. Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, China

    Hao Liu, Ke Li & Daocheng Wu

  2. Department of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA

    Hao Liu & Liang Xu

  3. Department of Radiation Oncology, The University of Kansas Cancer Center, Kansas City, KS, USA

    Liang Xu

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  1. Hao Liu
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  2. Ke Li
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Correspondence to Daocheng Wu.

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Liu, H., Li, K., Xu, L. et al. Bilayered near-infrared fluorescent nanoparticles based on low molecular weight PEI for tumor-targeted in vivo imaging. J Nanopart Res 16, 2784 (2014). https://doi.org/10.1007/s11051-014-2784-5

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