Controlled delivery of protoporphyrin IX precursors for photodynamic therapy of tumors using water soluble polymer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F25%3A10500950" target="_blank" >RIV/00216208:11310/25:10500950 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.epf2025.org/" target="_blank" >https://www.epf2025.org/</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Controlled delivery of protoporphyrin IX precursors for photodynamic therapy of tumors using water soluble polymer

Popis výsledku v původním jazyce

Among anticancer therapies, photodynamic therapy (PDT) is an advantageous approach thanks to its noninvasive character and low side effects. Its principle is based on using a photosensitizer, light and presence of oxygen to generate singlet oxygen leading to cell death. However, common photosensitizers still lack tumor targeting properties as well as prolonged blood circulation. An example of such photosensitizer is protoporphyrin IX (PPIX), which is often administered not itself, but in form of a prodrug, 5-aminolevulinic acid (5-ALA), which is metabolized to PPIX inside the cells. To overcome the poor pharmacokinetics of 5-ALA, we designed new nanomedicines based on covalently conjugated 5-ALA or its hexylester (HAL) to a water soluble copolymer of poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA). Water soluble polymer conjugates based on PHPMA have been used successfully for the delivery of many anticancer agents (2) relying on the enhanced permeability and retention (EPR) effect enabling high accumulation of the polymer conjugate in the tumor tissue. Herein, we present the synthesis of the nanomedicines by controlled radical polymerization with subsequent conjugation of 5-ALA/HAL via a pH sensitive hydrazone bond. Such nanomedicines present desired physico-chemical properties, pH sensitive release of 5-ALA/HAL and superior anticancer efficacy in vivo after irradiation.

Název v anglickém jazyce

Controlled delivery of protoporphyrin IX precursors for photodynamic therapy of tumors using water soluble polymer

Popis výsledku anglicky

Among anticancer therapies, photodynamic therapy (PDT) is an advantageous approach thanks to its noninvasive character and low side effects. Its principle is based on using a photosensitizer, light and presence of oxygen to generate singlet oxygen leading to cell death. However, common photosensitizers still lack tumor targeting properties as well as prolonged blood circulation. An example of such photosensitizer is protoporphyrin IX (PPIX), which is often administered not itself, but in form of a prodrug, 5-aminolevulinic acid (5-ALA), which is metabolized to PPIX inside the cells. To overcome the poor pharmacokinetics of 5-ALA, we designed new nanomedicines based on covalently conjugated 5-ALA or its hexylester (HAL) to a water soluble copolymer of poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA). Water soluble polymer conjugates based on PHPMA have been used successfully for the delivery of many anticancer agents (2) relying on the enhanced permeability and retention (EPR) effect enabling high accumulation of the polymer conjugate in the tumor tissue. Herein, we present the synthesis of the nanomedicines by controlled radical polymerization with subsequent conjugation of 5-ALA/HAL via a pH sensitive hydrazone bond. Such nanomedicines present desired physico-chemical properties, pH sensitive release of 5-ALA/HAL and superior anticancer efficacy in vivo after irradiation.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10404 - Polymer science

Projekt

<a href="/cs/project/LX22NPO5102" target="_blank" >LX22NPO5102: Národní ústav pro výzkum rakoviny</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů