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Passive and electro-assisted delivery of hydrogel nanoparticles in solid tumors, visualized by optical and magnetic resonance imaging in vivo

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Abstract

The present study describes a development of nanohydrogel, loaded with QD705 and manganese (QD705@Nanogel and QD705@Mn@Nanogel), and its passive and electro-assisted delivery in solid tumors, visualized by fluorescence imaging and magnetic resonance imaging (MRI) on colon cancer-grafted mice as a model. QD705@Nanogel was delivered passively predominantly into the tumor, which was visualized in vivo and ex vivo using fluorescent imaging. The fluorescence intensity increased gradually within 30 min after injection, reached a plateau between 30 min and 2 h, and decreased gradually to the baseline within 24 h. The fluorescence intensity in the tumor area was about 2.5 times higher than the background fluorescence. A very weak fluorescent signal was detected in the liver area, but not in the areas of the kidneys or bladder. This result was in contrast with our previous study, indicating that FITC@Mn@Nanogel did not enter into the tumor and was detected rapidly in the kidney and bladder after i.v. injection [J. Mater. Chem. B 2013, 1, 4932–4938]. We found that the embedding of a hard material (as QD) in nanohydrogel changes the physical properties of the soft material (decreases the size and negative charge and changes the shape) and alters its pharmacodynamics. Electroporation facilitated the delivery of the nanohydrogel in the tumor tissue, visualized by fluorescent imaging and MRI. Strong signal intensity was recorded in the tumor area shortly after the combined treatment (QD@Mn@Nanogel + electroporation), and it was observed even 48 h after the electroporation. The data demonstrate more effective penetration of the nanoparticles in the tumor due to the increased permeability of blood vessels at the electroporated area. There was no rupture of blood vessels after electroporation, and there were no artifacts in the images due to a bleeding.

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Acknowledgments

The authors thank Ms. Sayaka Shibata (Molecular Imaging Center, National Institute of Radiological Sciences, Japan) for her assistance during the experiments in vivo, Mr. Yoshikazu Ozawa for his assistance during the MRI measurements, and the One-stop Sharing Faculty Center for Future Drug Discoveries in the University of Tokyo for AFM measurements. The study was partially supported by the Ministry of Education, Science and Technology of Japan (Grant-in-Aid “Kakenhi” to R.B. and S.M., and JSPS Fellowship to B.N.) and conducted by the EU-COST Action TD1104.

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Authors and Affiliations

  1. Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan

    Rumiana Bakalova, Shuhei Murayama, Ichio Aoki & Tsuneo Saga

  2. Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, 21 Acad. G. Bonchev Str., Sofia, 1113, Bulgaria

    Biliana Nikolova, Severina Atanasova, Zhivko Zhelev & Iana Tsoneva

  3. Medical Faculty, Trakia University, 11 Armejska Str., Stara Zagora, 6000, Bulgaria

    Zhivko Zhelev

  4. Graduate School of Pharmaceutical Sciences and GPLII Program, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Masaru Kato

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  1. Rumiana Bakalova
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  2. Biliana Nikolova
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  3. Shuhei Murayama
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  4. Severina Atanasova
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  5. Zhivko Zhelev
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  6. Ichio Aoki
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  8. Iana Tsoneva
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  9. Tsuneo Saga
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Correspondence to Rumiana Bakalova.

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Author contributions

R.B., Z.Z., and I.A. designed the study; B.N., S.A., S.M., and M.K. performed the experiments; R.B., B.N., and S.A. analyzed the data; R.B. and B.N. wrote the manuscript; and Z.Z., I.T., and T.S. revised the manuscript.

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The authors report no conflicts of interest in this work.

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Bakalova, R., Nikolova, B., Murayama, S. et al. Passive and electro-assisted delivery of hydrogel nanoparticles in solid tumors, visualized by optical and magnetic resonance imaging in vivo. Anal Bioanal Chem 408, 905–914 (2016). https://doi.org/10.1007/s00216-015-9182-4

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  • DOI: https://doi.org/10.1007/s00216-015-9182-4

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