HPMA copolymer conjugated 5-aminolevulinic acid exhibits superior efficacy for photodynamic therapy with tumor-responsive and targeting properties

Rayhanul Islam, Kevin Kotalík, Vladimír Šubr, Shanghui Gao, Kazumi Yokomizo, Tomáš Etrych*, Jun Fang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
13 Downloads (Pure)

Abstract

In this study, we developed a nanoformulation of 5-aminolevulinic acid (5-ALA) for tumor-targeted photodynamic therapy, in which 5-ALA was conjugated with a biocompatible polymer N-(2-hydroxypropyl)methacrylamide (HPMA) through the hydrazone bond, i.e., P-ALA. P-ALA behaves as the nano-sized molecule with an average size of 5.5 nm in aqueous solution. P-ALA shows a largely increased release rate in acidic pH than physiological pH, suggesting the rapid release profile in acidic tumor environment. P-ALA did not show apparent cytotoxicity up to 0.1 mg/ml, however, under light irradiation, remarkable cell death was induced with the IC50 of 20–30 μg/ml. More importantly, we found significantly higher tumor accumulation of P-ALA than 5-ALA which benefit from its nano-size by taking advantage of the enhanced permeability and retention (EPR) effect. Consequently, P-ALA exhibited much improved in vivo antitumor efficacy without any apparent side effects. We thus anticipate the application of P-ALA as a nano-designed photosensitizer for anticancer photodynamic therapy.

Original languageEnglish
Article number102636
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume48
Early online date23 Dec 2022
DOIs
Publication statusPublished - Feb 2023
Externally publishedYes

Bibliographical note

Funding Information:
Funding sources: This work was supported by the research fund from Sojo University to J. Fang. and partly by a Grant-in-Aid for Scientific Research on Scientific Research (C) (JSPS KAKENHI grant numbers 19K09806 and 19K07743 ) to J. Fang. This work was also supported by the Czech Academy of Sciences [Mobility plus project JSPS-22-01 ] and by the project National Institute for Cancer Research (Programme EXCELES, ID project no. LX22NPO5102 ) - Funded by the European Union – Next Generation E.

Publisher Copyright:
© 2022 The Authors

Keywords

  • 5-Aminolevulinic acid
  • EPR effect
  • HPMA copolymer
  • Photodynamic therapy
  • Tumor targeting

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • General Materials Science
  • Pharmaceutical Science

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