Drug Delivery and Translational Research

, Volume 5, Issue 1, pp 38–50 | Cite as

Medicinal facilities to B16F10 melanoma cells for distant metastasis control with a supramolecular complex by DEAE-dextran-MMA copolymer/paclitaxel

  • Yuki Eshita
  • Rui-Cheng Ji
  • Masayasu Onishi
  • Takashi Kobayashi
  • Masaaki Mizuno
  • Jun Yoshida
  • Naoji Kubota
  • Yasuhiko Onishi
Research Article


The resistance of cancer cells to chemotherapeutic drugs (MDR) is a major problem to be solved. A supramolecular DEAE-dextran-MMA copolymer (DDMC)/paclitaxel (PTX) complex was obtained by using PTX as the guest and DDMC as the host having 50–300 nm in diameter. The drug resistance of B16F10 melanoma cells to paclitaxel was observed, but there is no drug resistance of melanoma cells to the DDMC/PTX complex in vitro. The cell death rate was determined using Michaelis–Menten kinetics, as the DDMC/PTX complex promoted allosteric supramolecular reaction to tubulin. The DDMC/PTX complex showed a very superior anti-cancer activity to paclitaxel alone in vivo. The median survival time (MST) of the saline, PTX, DDMC/PTX4 (particle size, 50 nm), and DDMC/PTX5 (particle size, 290 nm) groups were 120 h (T/C, 1.0), 176 h (T/C, 1.46), 328 h (T/C, 2.73), and 280 h (T/C, 2.33), respectively. The supramolecular DDMC/PTX complex showed the twofold effectiveness of PTX alone (p < 0.036). Histochemical analysis indicated that the administration of DDMC/PTX complex decreased distant metastasis and increased the survival of mice. A mouse of DDMC/PTX4 group in vivo was almost curing after small dermatorrhagia owing to its anti-angiogenesis, and it will be the hemorrhagic necrotic symptom of tumor by the release of “tumor necrosis factor alpha (TNF-α)” cytokine. As the result, the medicinal action of the DDMC/PTX complex will suppress the tumor-associated action of M2 macrophages and will control the metastasis of cancer cells.


DEAE-dextran-MMA copolymer Paclitaxel Melanoma cells Metastatic spread Lymphatic vessel density M2 macrophages 





DEAE-dextran-MMA copolymer


Cell death


Enhanced permeation and retention


Reticuloendothelial system


Drug delivery system


Poly(methyl methacrylate)



A portion of this research was carried out with the support of a Japanese Ministry of Health, Labor, and Welfare Scientific Research Grant (H26-Shinko Jitsuyoka-Ippan-007) and the Japan Society for the Promotion of Science Research Grant (Basic B 25300053).

Conflicts of interest

No potential conflicts of interest were disclosed.


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Copyright information

© Controlled Release Society 2014

Authors and Affiliations

  1. 1.Department of Infectious Disease Control, Faculty of MedicineOita UniversityYufuJapan
  2. 2.Department of Human Anatomy, Faculty of MedicineOita UniversityYufuJapan
  3. 3.The Center for Advanced Medicine and Clinical ResearchNagoya University HospitalNagoyaJapan
  4. 4.Japan Labour Health and Welfare OrganizationChubu Rosai HospitalNagoyaJapan
  5. 5.Department of Chemistry, Faculty of MedicineOita UniversityYufuJapan
  6. 6.Ryujyu Science CorporationSetoJapan

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