Quantum dot/nitroxide-based sensing platform for image-guided drug delivery in cancer

• Project/Area Number: 24510321
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical biology
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: RUMIANA Bakalova 独立行政法人放射線医学総合研究所, 分子イメージング研究センター, 主任研究員 (30469936)
• Co-Investigator(Kenkyū-buntansha): AOKI Ichio (ZHELEV Zhivko) 独立行政法人放射線医学総合研究所, 分子イメージング研究センター, チームリーダー (10319519)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2014: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: Polymersomes / Quantum dots / Nitroxides / Drug delivery systems / Cancer / 量子ドッド / ニトロキシラジカル / DDS / 蛍光イメージング / in vivo イメージング / 腫瘍 / MRI / drug-delivery systems / nanoparticles / polymersomes / quantum dot / nitroxides / fluorescent imaging / EPR imaging / cancer / ニトロキシルラジカル / レドックス / 酸化還元 / 量子ドット / センサー / 蛍光 / 反応性造影剤

Outline of Final Research Achievements

We developed polymersomes, embedding with quantum dots (QDs) and hydrophobic nitroxide-labeled anticancer drug, as a new sensing platform for imaging of drug delivery in cancer. If both substances are retained into the polymersome, there is no fluorescence of QDs. If nitroxide-labeled drug is released from polymersomes, the fluorescence of QDs appeared.
On experimental cancer-bearing animals, using optical imaging, we established that these nanoparticles were appropriate for imaging of cancer, lymph node mapping, as well as for imaging of drug delivery. A strong fluorescent signal, corresponding to QD705 fluorescence, was detected in the tumor, as well as into the lymph nodes. The half-life of QD/nitroxide-embeding polymersomes was 6±2 hours in the bloodstream, 8±2 hours into the tumor and 11±3 hours in the lymph nodes. The data suggests these size-controlled long-circulating polymersomes are useful matrix for development of nano-formulations with theranostic capabilities.

Research Products

• [Journal Article] Lymph node mapping using quantum dot-labeled polymersomes. (2015)
  • Author(s): Bakalova R., Z. Zhelev, B. Nikolova, S. Murayama, I. Tsoneva, I. Aoki, T. Saga.
  • Journal Title: Gen. Physiol. Biophys. Volume: 0 Pages: 0-0
  • Peer Reviewed
• [Journal Article] Delivery of size-controlled long-circulating polymersomes in solid tumors, visualized by quantum dots and optical imaging in vivo (2014)
  • Author(s): 2.Bakalova R., D. Lazarova, B. Nikolova, S. Atanasova, G. Zlateva, Z. Zhelev, and I. Aoki.
  • Journal Title: Biotechnol. Biotechnol. Equip Volume: 0 Pages: 0-0
  • Peer Reviewed
• [Journal Article] In vivo visualization of electro-assisted delivery of nanoparticles in cancer using optical imaging, (2014)
  • Author(s): 3.Atanasova S., D. Lazarova, B. Nikolova, Z. Zhelev, T. Tsoneva, I. Aoki, and R. Bakalova
  • Journal Title: Anticancer Res. Volume: 34 Pages: 5819-5821
  • Peer Reviewed
• [Journal Article] Delivery of size-controlled long-circulating polymersomes in solid tumors, visualized by quantum dots and optical imaging in vivo. (2014)
  • Author(s): R. Bakalova, Z. Zhelev, D. Lazarova, I. Aoki, T. Saga.
  • Journal Title: Biotechnol. Biotechnol. Equip. Volume: 0 Pages: 0-0
  • Peer Reviewed
• [Journal Article] Tissue redox activity as a hallmark of carcinogenesis: from early to terminal stages of cancer. (2013)
  • Author(s): Z. Zhelev, R. Bakalova, I. Aoki, T. Saga.
  • Journal Title: Clin. Cancer Res., Volume: 19（９） Pages: 2503-2517
  • Peer Reviewed
• [Journal Article] Tissue redox activity as a sensing platform for imaging of cancer based on nitroxide redox cycle. (2013)
  • Author(s): Z. Zhelev, I. Aoki, V. Gadjeva, B. Nikolova, R. Bakalova, T. Saga.
  • Journal Title: Eur. J. Cancer Volume: 49（６） Issue: 6 Pages: 1467-1478
  • DOI: 10.1016/j.ejca.2012.10.026
  • Peer Reviewed
• [Journal Article] Cell-penetrating nitroxides as molecular sensors for imaging of cancer in vivo, based on tissue redox activity (2012)
  • Author(s): Zhelev Z, Gadjeva V, Aoki I, Bakalova R, Saga T
  • Journal Title: Molecular BioSystems Volume: 8 Issue: 10 Pages: 2733-2740
  • DOI: 10.1039/c2mb25128k
  • Peer Reviewed
• [Presentation] In vivo visualization of electro-assisted delivery of nanoparticles in cancer using optical imaging (2014)
  • Author(s): 2.Atanasova S., D. Lazarova, B. Nikolova, Z. Zhelev, T. Tsoneva, I. Aoki, and R. Bakalova
  • Organizer: 9th International Conference of Anticancer Research,
  • Place of Presentation: Sithonia, Greece,
  • Year and Date: 2014-10-06 – 2014-10-10
• [Presentation] In vitro analysis of redox status of normal and tumor cells using nitroxide radicals and EPR spectroscopy (2014)
  • Author(s): 3.Georgieva E., D. Ivanova, D. Lazarova, R. Bakalova, I. Aoki, and Z. Zhelev
  • Organizer: 9th International Conference of Anticancer Research
  • Place of Presentation: Sithonia, Greece,
  • Year and Date: 2014-10-06 – 2014-10-10
• [Presentation] Systematic study on the cytotoxic and/or cytostatic effects of over twenty anticancer drugs: The crucial importance of the analytical approach and data processing (2014)
  • Author(s): 4.Ivanova D., D. Lazarova, E. Georgieva, I. Aoki, Z. Zhelev, and R. Bakalova
  • Organizer: 9th International Conference of Anticancer Research
  • Place of Presentation: Sithonia, Greece,
  • Year and Date: 2014-10-06 – 2014-10-10
• [Presentation] Electro-assisted drug delivery in cancer using size-controlled long-circulating polymer nanoparticles, (2014)
  • Author(s): 1.Atanasova S., D. Lazarova, B. Nikolova, Z. Zhelev, Y. Tsoneva, L. Spasov, and R. Bakalova
  • Organizer: 24th International Conference of the Society of Bulgarian Scientists
  • Place of Presentation: Stara Zagora, Bulgaria
  • Year and Date: 2014-06-06 – 2014-06-07
• [Presentation] Tissue redox activity as a sensing platform for imaging of cancer, based on nitroxide redox ｃｙｃle. (2013)
  • Author(s): 2. Bakalova R., Z. Zhelev, I. Aoki, D. Kokuryo,V. Gadjeva, and T. Saga.
  • Organizer: ISMRM 21st Annual Meeting and Exhibition,
  • Place of Presentation: Salt Lake, Utah, US,
• [Presentation] Imaging of Tissue redox activity from early to terminal stage of cancer development using nitroxide enhanced MRI. (2013)
  • Author(s): 3. Bakalova R., Z. Zhelev, D. Kokuryo,. I. Aoki, V, Gadjeva, and T. Saga.
  • Organizer: 6th World Molecular Imaging Congress,
  • Place of Presentation: Savannah, Georgia, USA,
• [Presentation] – Delivery of quantum dots in cancer using size-controlled long-circulating polymersomes, International Conference “Bioscience – (2013)
  • Author(s): 4. Lazarova D., Z. Zhelev, G. Zlateva, I. Aoki, and R. Bakalova.
  • Organizer: Development and New Opportunities
  • Place of Presentation: Sofia, Bulgaria.
• [Presentation] Cell-penetrating nitroxides, but not non-penetrating, are molecular sensors for imaging of cancer in vivo based on tissue redox activity (2012)
  • Author(s): Bakalova R, Zhelev Z, Gadjeva V, Aoki I, Kokuryo D, Saga T
  • Organizer: 第7回日本分子イメージング学会
  • Place of Presentation: 浜松
• [Presentation] Tissue Redox Activity as a Sensing Platform for Magnetic Resonance Imaging of Cancer: Diagnostic and Therapeutic Aspects (2012)
  • Author(s): Bakalova R., Zhelev Z., Kokuryo D., Aoki I., Gadjeva V., Saga T
  • Organizer: World Molecular Imaging Congress 2012
  • Place of Presentation: Dublin, Ireland