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HPMA copolymer conjugated 5-aminolevulinic acid exhibits superior efficacy for photodynamic therapy with tumor-responsive and targeting properties
- 1.0565942 - ÚMCH 2024 RIV US eng J - Journal Article
Islam, R. - Kotalík, Kevin - Šubr, Vladimír - Gao, S. - Zhou, J.-R. - Yokomizo, K. - Etrych, Tomáš - Fang, J.
HPMA copolymer conjugated 5-aminolevulinic acid exhibits superior efficacy for photodynamic therapy with tumor-responsive and targeting properties.
Nanomedicine: Nanotechnology, Biology and Medicine. Roč. 48, February (2023), č. článku 102636. ISSN 1549-9634. E-ISSN 1549-9642
R&D Projects: GA MŠMT LX22NPO5102
Grant - others:AV ČR(CZ) JSPS-22-01
Program: Bilaterální spolupráce
Institutional support: RVO:61389013
Keywords : HPMA copolymer * 5-aminolevulinic acid * photodynamic therapy
OECD category: Polymer science
Impact factor: 4.2, year: 2023
Method of publishing: Open access
https://www.sciencedirect.com/science/article/pii/S1549963422001228?via%3Dihub
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.
Permanent Link: https://hdl.handle.net/11104/0337420
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