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Research ArticleExperimental Studies

Preparation of Micelles Encapsulating Doxorubicin and Their Anticancer Effect in Combination With Tranilast in 3D Spheroids and In Vivo

TERUKI NII, KANJI YOSHIKAWA, ISSEI TAKEUCHI and KIMIKO MAKINO
Anticancer Research June 2022, 42 (6) 2847-2857; DOI: https://doi.org/10.21873/anticanres.15766
TERUKI NII
1Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Fukuoka, Japan;
2Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan;
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  • For correspondence: nii.teruki.204@m.kyushu-u.ac.jp itakeuchi@iju.ac.jp
KANJI YOSHIKAWA
3Faculty of Pharmaceutical Sciences, Tokyo University of Sciences, Noda, Japan;
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ISSEI TAKEUCHI
3Faculty of Pharmaceutical Sciences, Tokyo University of Sciences, Noda, Japan;
4Center for Drug Delivery Research, Tokyo University of Sciences, Noda, Japan;
5Josai International University, Togane, Japan
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  • For correspondence: nii.teruki.204@m.kyushu-u.ac.jp itakeuchi@iju.ac.jp
KIMIKO MAKINO
3Faculty of Pharmaceutical Sciences, Tokyo University of Sciences, Noda, Japan;
4Center for Drug Delivery Research, Tokyo University of Sciences, Noda, Japan;
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Abstract

Background/Aim: The objective of this study was to prepare doxorubicin encapsulated in micelles (DOX-micelles) using poly(hexadecanyloxyethylene glycol-lactate phosphate), which we recently synthesized, and to evaluate the anticancer effect of DOX-micelles in vitro and in vivo. Materials and Methods: To evaluate the anticancer effect of DOX-micelles in vitro, three-dimensional spheroids composed of B16 mouse melanoma cells and fibroblasts were prepared by changing the ratio of cancer cells to fibroblasts. In addition, for efficient doxorubicin treatment of the cells present in the center of the spheroids, tranilast, an anti-fibrotic drug was added to the spheroids before treatment with DOX-micelles, then the amount of doxorubicin and cell viability of spheroids were evaluated. Moreover, to assess the effects of the combination of DOX-micelles with tranilast in vivo, relative tumor volume was investigated in a mouse model of melanoma. Results: The mean diameter and doxorubicin content of DOX-micelles were 93.3 nm and 3.5%, respectively. When the ratio of cancer cells to fibroblasts was 20:80, spheroids with spherical and rigid shapes were obtained. In addition, the amount of doxorubicin in the spheroids was increased by tranilast treatment, and an efficient anticancer effect was also observed. The anticancer effect of the combination of tranilast and DOX-micelles was confirmed in vivo. Conclusion: Micelles encapsulating doxorubicin are promising for cancer therapy, and their anticancer effect is improved by tranilast pretreatment in 3D spheroids in vivo.

Key Words:
  • Micelles
  • pH-responsive
  • three-dimensional cell culture
  • tumor microenvironment
  • anti-fibrotic drug
  • tumor-bearing mice
  • Received March 25, 2022.
  • Revision received April 11, 2022.
  • Accepted April 14, 2022.
  • Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 42 (6)
Anticancer Research
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June 2022
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Preparation of Micelles Encapsulating Doxorubicin and Their Anticancer Effect in Combination With Tranilast in 3D Spheroids and In Vivo
TERUKI NII, KANJI YOSHIKAWA, ISSEI TAKEUCHI, KIMIKO MAKINO
Anticancer Research Jun 2022, 42 (6) 2847-2857; DOI: 10.21873/anticanres.15766

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Preparation of Micelles Encapsulating Doxorubicin and Their Anticancer Effect in Combination With Tranilast in 3D Spheroids and In Vivo
TERUKI NII, KANJI YOSHIKAWA, ISSEI TAKEUCHI, KIMIKO MAKINO
Anticancer Research Jun 2022, 42 (6) 2847-2857; DOI: 10.21873/anticanres.15766
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Keywords

  • Micelles
  • pH-responsive
  • three-dimensional cell culture
  • tumor microenvironment
  • anti-fibrotic drug
  • tumor-bearing mice
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