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Technetium-99m and ICG-labeled HPG (hyperbranched polyglycerol) as a SPECT/FL dual imaging nanoprobe for imaging blood cells: in vitro investigation using myelogenous leukemia cells

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Abstract

This study aimed to develop a single photo emission computed tomography/fluorescence (SPECT/FL) bimodal imaging probe to image blood cells. Hyperbranched polyglycerol (HPG) was synthesized by anionic ring-opening polymerization. Succinic anhydride was used to functionalize HPG. Then, indocyanine green (ICG) was bound to HPG, with a 73.59% binding yield. Deferoxamine (DFO) was subsequently bound to ICG-HPG, and DFO-ICG-HPG was radiolabeled with technetium-99m, with 100% yield. The molecular weight of HPG in this study was found to be 6.8 kDa. In in vitro studies, the radiolabeled nanoconjugates remained stable even after 6 h (last timepoint when stability was assessed), and when the nanoconjugates were applied to K562 chronic myeloid leukemia cells, the highest cell viability was observed at a concentration of 5 µg/mL and binding efficiency increased over time, reaching 30% at 6 h (last timepoint when binding efficiency was assessed). The results support the feasibility of the developed probe to image blood cells, which would be useful for applications such as detecting internal bleeding.

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References

  1. Nguyen QT, Tsien RY (2013) Fluorescence-guided surgery with live molecular navigation—a new cutting edge. Nat Rev Cancer 13(9):653–662. https://doi.org/10.1038/nrc3566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Grady E (2016) Gastrointestinal bleeding scintigraphy in the early 21st century. J Nucl Med 57(2):252–259. https://doi.org/10.2967/jnumed.115.157289

    Article  CAS  PubMed  Google Scholar 

  3. Licha K, Welker P, Weinhart M, Wegner N, Kern S, Reichert S, Gemeinhardt I, Weissbach C, Ebert B, Haag R, Schirner M (2011) Fluorescence imaging with multifunctional polyglycerol sulfates: novel polymeric near-IR probes targeting inflammation. Bioconjug Chem 22(12):2453–2460. https://doi.org/10.1021/bc2002727

    Article  CAS  PubMed  Google Scholar 

  4. Biffi S, Dal Monego S, Dullin C, Garrovo C, Bosnjak B, Licha K, Welker P, Epstein MM, Alves F (2013) Dendritic polyglycerolsulfate near infrared fluorescent (NIRF) dye conjugate for non-invasively monitoring of inflammation in an allergic asthma mouse model. PLoS ONE 8(2):e57150. https://doi.org/10.1371/journal.pone.0057150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kainthan RK, Hester SR, Levin E, Devine DV, Brooks DE (2007) In vitro biological evaluation of high molecular weight hyperbranched polyglycerols. Biomaterials 28(31):4581–4590. https://doi.org/10.1016/j.biomaterials.2007.07.011

    Article  CAS  PubMed  Google Scholar 

  6. Chapanian R, Constantinescu I, Brooks DE, Scott MD, Kizhakkedathu JN (2012) In vivo circulation, clearance, and biodistribution of polyglycerol grafted functional red blood cells. Biomaterials 33(10):3047–3057. https://doi.org/10.1016/j.biomaterials.2011.12.053

    Article  CAS  PubMed  Google Scholar 

  7. Rossi NAA, Constantinescu I, Kainthan RK, Brooks DE, Scott MD, Kizhakkedathu JN (2010) Red blood cell membrane grafting of multi-functional hyperbranched polyglycerols. Biomaterials 31(14):4167–4178. https://doi.org/10.1016/j.biomaterials.2010.01.137

    Article  CAS  PubMed  Google Scholar 

  8. Kainthan RK, Brooks DE (2007) In vivo biological evaluation of high molecular weight hyperbranched polyglycerols. Biomaterials 28(32):4779–4787. https://doi.org/10.1016/j.biomaterials.2007.07.046

    Article  CAS  PubMed  Google Scholar 

  9. Kainthan RK, Muliawan EB, Hatzikiriakos SG, Brooks DE (2006) Synthesis, characterization, and viscoelastic properties of high molecular weight hyperbranched polyglycerols. Macromolecules 39(22):7708–7717. https://doi.org/10.1021/ma0613483

    Article  CAS  Google Scholar 

  10. Shen Y, He G, Guo Y, Xie H, Fang W (2017) Modified hyperbranched polyglycerol as dispersant for size control and stabilization of gold nanoparticles in hydrocarbons. Nanoscale Res Lett 12(1):525. https://doi.org/10.1186/s11671-017-2296-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wilms D, Wurm F, Nieberle J, Böhm P, Kemmer-Jonas U, Frey H (2009) Hyperbranched polyglycerols with elevated molecular weights: a facile two-step synthesis protocol based on polyglycerol macroinitiators. Macromolecules 42(9):3230–3236. https://doi.org/10.1021/ma802701g

    Article  CAS  Google Scholar 

  12. Wang H, Li X, Tse BW-C, Yang H, Thorling CA, Liu Y, Touraud M, Chouane JB, Liu X, Roberts MS, Liang X (2018) Indocyanine green-incorporating nanoparticles for cancer theranostics. Theranostics 8(5):1227–1242. https://doi.org/10.7150/thno.22872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hirosuke H, Toyota T, Hayashi H, Nomoto T, Fujinami M (2014) Application of a novel near infrared-fluorescence giant vesicle- and polymerasome-based tissue marker for endoscopic and laparoscopic navigation. Anal Sci 30(2):225–230. https://doi.org/10.2116/analsci.30.225

    Article  Google Scholar 

  14. Imran ul-haq M, Hamilton JL, Lai BFL, Shenoi, RA, Horte, S, Constantinescu, I, Leitch, HA, Kizhakkedathu, JN (2013) Design of long circulating nontoxic dendritic polymers for the removal of iron in vivo. ACS Nano 7(12):10704–10716. https://doi.org/10.1021/nn4035074

  15. Silliman CC, Peterson VM, Mellman DL, Dixon DJ, Hambidge KM, Lane PA (1993) Iron chelation by deferoxamine in sickle cell patients with severe transfusion-induced hemosiderosis: a randomized, double-blind study of the dose-response relationship. J Lab Clin Med 122(1):48–54

    CAS  PubMed  Google Scholar 

  16. Tyagi P, Kumar A, Gupta D, Singh H (2017) Decorporation of iron metal using dialdehyde cellulose-deferoxamine microcarrier. AAPS PharmSciTech 18(1):156–165. https://doi.org/10.1208/s12249-016-0499-x

    Article  CAS  PubMed  Google Scholar 

  17. Hallaway PE, Eaton JW, Panter SS, Hedlund BE (1989) Modulation of deferoxamine toxicity and clearance by covalent attachment to biocompatible polymers. Proc Natl Acad Sci 86(24):10108–10112. https://doi.org/10.1073/pnas.86.24.10108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mousa SA, Ritger RC, Smith RD (1992) Efficacy and safety of deferoxamine conjugated to hydroxyethyl starch. J Cardiovasc Pharmacol 19(3):425–429. https://doi.org/10.1097/00005344-199203000-00019

    Article  CAS  PubMed  Google Scholar 

  19. Poitou J, Rizzo-Padoin N, Trouvin J-H, Matillon Y, Deletraz-Delporte M (2020) La cellule sanguine marquée par un radionucléide : recherche d’une qualification juridique. Ann Pharm Françaises 78(1):49–57. https://doi.org/10.1016/j.pharma.2019.09.001

    Article  CAS  Google Scholar 

  20. Power D, Larson I, Hartley P, Dunstan D, Boger DV (1998) Atomic force microscopy studies on hydroxypropylguar gels formed under shear. Macromolecules 31(25):8744–8748. https://doi.org/10.1021/ma971033a

    Article  CAS  Google Scholar 

  21. Li M, Liu L, Xi N, Wang YC, Dong ZL, Xiao XB, Zhang WJ (2012) Atomic force microscopy imaging and mechanical properties measurement of red blood cells and aggressive cancer cells. Sci China Life Sci 55(11):968–973. https://doi.org/10.1007/s11427-012-4399-3

    Article  PubMed  Google Scholar 

  22. Ye L, Letchford K, Heller M, Liggins R, Guan D, Kizhakkedathu JN, Brooks DE, Jackson JK, Burt HM (2011) Synthesis and characterization of carboxylic acid conjugated, hydrophobically derivatized, hyperbranched polyglycerols as nanoparticulate drug carriers for cisplatin. Biomacromolecules 12(1):145–155. https://doi.org/10.1021/bm101080p

  23. Yang H-M, Choi HM, Jang S-C, Han MJ, Seo BK, Moon JK, Lee KW (2015) Succinate functionalization of hyperbranched polyglycerol-coated magnetic nanoparticles as a draw solute during forward osmosis. J Nanosci Nanotechnol 15(10):8279–8284. https://doi.org/10.1166/jnn.2015.11244

    Article  CAS  PubMed  Google Scholar 

  24. Umemura M, Kim J-H, Aoyama H, Hoshino Y, Fukumura H, Nakakaji R, Sato I, Ohtake M, Akimoto T, Narikawa M, Tanaka R, Fujita T, Yokoyama U, Taguri M, Okumura S, Sato M, Eguchi H, Ishikawa Y (2017) The iron chelating agent, deferoxamine detoxifies Fe(Salen)-induced cytotoxicity. J Pharmacol Sci 134(4):203–210. https://doi.org/10.1016/j.jphs.2017.07.002

    Article  CAS  PubMed  Google Scholar 

  25. Jafari M, Abolmaali SS, Najafi H, Tamaddon AM (2020) Hyperbranched polyglycerol nanostructures for anti-biofouling, multifunctional drug delivery, bioimaging and theranostic applications. Int J Pharm 576:118959. https://doi.org/10.1016/j.ijpharm.2019.118959

    Article  CAS  PubMed  Google Scholar 

  26. Son S, Shin E, Kim B-S (2015) Redox-degradable biocompatible hyperbranched polyglycerols: synthesis, copolymerization kinetics, degradation, and biocompatibility. Macromolecules 48(3):600–609. https://doi.org/10.1021/ma502242v

    Article  CAS  Google Scholar 

  27. de Queiroz AAA, Bressiani JC, Bressiani AHA, Higa OZ, Abraham GA (2008) A novel bone scaffolds based on hyperbranched polyglycerol fibers filled with hydroxyapatite nanoparticles. in vitro cell response. Key Eng Mater 396–398:633–636. https://doi.org/10.4028/www.scientific.net/KEM.396-398.633

    Article  Google Scholar 

  28. Schmitt V, Rodríguez-Rodríguez C, Hamilton JL et al (2018) Quantitative SPECT imaging and biodistribution point to molecular weight independent tumor uptake for some long-circulating polymer nanocarriers. RSC Adv 8(10):5586–5595. https://doi.org/10.1039/C7RA09183D

    Article  CAS  Google Scholar 

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Acknowledgements

This work was financially supported by Ege University Research Fund (2018 FBE 006) and partially presented at HEZARFEN International Congress of Science, Mathematics, and Engineering Sciences held in Izmir/Turkey on November 8-10, 2019. Dr. Omer Aras was partially supported through the NIH/NCI Cancer Support Grant P30 CA008748.

Funding

Ege Üniversitesi,2018 FBE 006, Perihan Unak; Division of Cancer Prevention,National Cancer Institute, P30 CA008748, Ömer Aras

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Authors and Affiliations

  1. Department of Nuclear Applications, Institute of Nuclear Sciences, Ege University, Bornova, Izmir, 35100, Turkey

    Sibel Ay, Volkan Yasakçı & Perihan Ünak

  2. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA

    Ömer Aras

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  1. Sibel Ay
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  2. Volkan Yasakçı
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Correspondence to Perihan Ünak.

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Ay, S., Yasakçı, V., Aras, Ö. et al. Technetium-99m and ICG-labeled HPG (hyperbranched polyglycerol) as a SPECT/FL dual imaging nanoprobe for imaging blood cells: in vitro investigation using myelogenous leukemia cells. J Radioanal Nucl Chem 331, 43–54 (2022). https://doi.org/10.1007/s10967-021-08122-y

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