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

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved..

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.

Media Type:

Electronic Article

Year of Publication:

2023

Publication:

2023

Contained In:

To Main Record - volume:48

Contained In:

Nanomedicine : nanotechnology, biology, and medicine - 48(2023) vom: 05. Feb., Seite 102636

Language:

English

Contributors:

Islam, Rayhanul [Author]
Kotalík, Kevin [Author]
Šubr, Vladimír [Author]
Gao, Shanghui [Author]
Zhou, Jian-Rong [Author]
Yokomizo, Kazumi [Author]
Etrych, Tomáš [Author]
Fang, Jun [Author]

Links:

Volltext

Keywords:

5-Aminolevulinic acid
80168379AG
88755TAZ87
Aminolevulinic Acid
Antineoplastic Agents
Doxorubicin
EPR effect
HPMA copolymer
Hydroxypropyl methacrylate
Journal Article
Photodynamic therapy
Polymers
Tumor targeting
UKW89XAX2X

Notes:

Date Completed 14.02.2023

Date Revised 14.02.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.nano.2022.102636

funding:

Supporting institution / Project title:

PPN (Catalogue-ID):

NLM35057166X