Development of Tumor-targeting Antitumor Agents Based on Polymer Effect

• Nakamura Hideaki

  Faculty of Pharmaceutical Sciences, Sojo University

Bibliographic Information

Other Title

• 高分子効果を基盤とする腫瘍集積性薬剤の開発研究
• Review for award 高分子効果を基盤とする腫瘍集積性薬剤の開発研究
• Review for award コウブンシ コウカ オ キバン ト スル シュヨウ シュウセキセイ ヤクザイ ノ カイハツ ケンキュウ

Abstract

Here the author describes the tumor-selective delivery of a fluorescence photosensitizing agent and an antitumor agent, based on the polymer effect of an N-(2-hydroxypropyl)methacrylamide (HPMA) based copolymer, by utilizing the enhanced permeability and retention (EPR) effect seen in solid tumors. Firstly, the tumor distribution of the photosensitizer, zinc-protoporphyrin IX (ZnPP), was significantly increased by conjugation with the HPMA polymer (P-ZnPP). The P-ZnPP suppressed tumor growth by local generation of cytotoxic singlet oxygen, and the tumor tissue was visualized by fluorescence upon light irradiation. Subsequently, a two-step mechanism for tumor selectivity was observed for the cytotoxic anthracycline, pirarubicin (THP), which conjugated the HPMA-based copolymer via a hydrazone bond (P-THP). The EPR-dependent accumulation of P-THP and the tumor-selective release of THP in the tumor tissues led to highly tumor-selective toxicity. Rapid cell uptake of THP compared to other anthracyclines, and deeper P-THP penetration of the tumor cell spheroid were attributed to the superior antitumor activity of P-THP. The molecular weight of P-THP affected its antitumor activity; oligomeric P-THP derivatives with higher molecular weights, DP-THP and SP-THP, showed even higher antitumor activity. P-THP was effective for both implanted tumor and autochthonous tumor models. These results indicate that nano-sized anticancer drugs based on polymer effect are promising clinical therapeutics.

Journal

• YAKUGAKU ZASSHI

  YAKUGAKU ZASSHI 140 (10), 1243-1249, 2020-10-01

  The Pharmaceutical Society of Japan

Keywords

• polymer effect
• enhanced permeability and retention effect
• anti-tumor therapy
• zinc-protoporphyrin IX
• pirarubicin

Details

• CRID: 1390848647560058880
• NII Article ID: 130007920206
• NII Book ID: AN00284903
• DOI: 10.1248/yakushi.20-00158
• ISSN: 13475231
• ISSN: 00316903
• NDL BIB ID: 030682725
• PubMed: 32999203
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I030682725
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/140/10/140_20-00158/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2021232921
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed