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

Research Paper

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.

Keywords

Near-infrared Fluorescence Nanoparticle Tumor-targeting In vivo imaging 

Notes

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.).

Supplementary material

11051_2014_2784_MOESM1_ESM.doc (2.2 mb)
Supplementary material 1 (DOC 2268 kb)

References

  1. 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 CrossRefGoogle Scholar
  2. 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
  3. Belguise-Valladier P, Behr JP (2001) Nonviral gene delivery: towards artificial viruses. Cytotechnology 35:197–201. doi: 10.1023/A:1013133605406 CrossRefGoogle Scholar
  4. 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 CrossRefGoogle Scholar
  5. 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 CrossRefGoogle Scholar
  6. 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 CrossRefGoogle Scholar
  7. 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 CrossRefGoogle Scholar
  8. 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 CrossRefGoogle Scholar
  9. 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
  10. 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 CrossRefGoogle Scholar
  11. 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 CrossRefGoogle Scholar
  12. 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 12:139–149Google Scholar
  13. 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 CrossRefGoogle Scholar
  14. Han J, Burgess K (2010) Fluorescent indicators for intracellular pH. Chem Rev 110:2709–2728. doi: 10.1021/cr900249z CrossRefGoogle Scholar
  15. 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 CrossRefGoogle Scholar
  16. 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 CrossRefGoogle Scholar
  17. 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 CrossRefGoogle Scholar
  18. 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 CrossRefGoogle Scholar
  19. 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 CrossRefGoogle Scholar
  20. 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 CrossRefGoogle Scholar
  21. 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 CrossRefGoogle Scholar
  22. Lakowicz JR (1999) Introduction to fluorescence. Principles of fluorescence spectroscopy. Springer, New York, pp 1–23CrossRefGoogle Scholar
  23. 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 CrossRefGoogle Scholar
  24. 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 CrossRefGoogle Scholar
  25. 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 CrossRefGoogle Scholar
  26. 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 CrossRefGoogle Scholar
  27. Necas J, Bartosikova L, Brauner P, Kolar J (2008) Hyaluronic acid (hyaluronan): a review. Vet Med-Czech 53:397–411Google Scholar
  28. 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 CrossRefGoogle Scholar
  29. 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 CrossRefGoogle Scholar
  30. 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 CrossRefGoogle Scholar
  31. 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 CrossRefGoogle Scholar
  32. 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 CrossRefGoogle Scholar
  33. 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 CrossRefGoogle Scholar
  34. 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 CrossRefGoogle Scholar
  35. 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 CrossRefGoogle Scholar
  36. 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 CrossRefGoogle Scholar
  37. 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 CrossRefGoogle Scholar
  38. 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 CrossRefGoogle Scholar
  39. 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 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and TechnologyXi’an Jiaotong UniversityXi’anChina
  2. 2.Department of Molecular BiosciencesThe University of KansasLawrenceUSA
  3. 3.Department of Radiation OncologyThe University of Kansas Cancer CenterKansas CityUSA

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