Polymeric material based on cystamine-protoporphyrin IX connection in PLGA of potential utility in photodynamic therapy - preparation, physicochemical properties, and biological activity

IF 4.7 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences Pub Date : 2025-07-18 DOI:10.1016/j.ejps.2025.107209

Patrycja Koza , Marcin Wysocki , Malgorzata Kucinska , Julia Pospieszna , Bartłomiej Kost , Maciej Stawny , Aleksander Smolarkiewicz-Wyczachowski , Dariusz T. Mlynarczyk , Marta Ziegler-Borowska , Tadeusz Biela , Lukasz Sobotta , Tomasz Koczorowski , Marek Murias , Tomasz Goslinski

{"title":"Polymeric material based on cystamine-protoporphyrin IX connection in PLGA of potential utility in photodynamic therapy - preparation, physicochemical properties, and biological activity","authors":"Patrycja Koza , Marcin Wysocki , Malgorzata Kucinska , Julia Pospieszna , Bartłomiej Kost , Maciej Stawny , Aleksander Smolarkiewicz-Wyczachowski , Dariusz T. Mlynarczyk , Marta Ziegler-Borowska , Tadeusz Biela , Lukasz Sobotta , Tomasz Koczorowski , Marek Murias , Tomasz Goslinski","doi":"10.1016/j.ejps.2025.107209","DOIUrl":null,"url":null,"abstract":"<div><div>By the use of suitable delivery systems and pharmaceutical formulations, improved transportation of photosensitizers to cancer cells in photodynamic therapy can be achieved. The aim of our study was to demonstrate controlled, redox-triggered release of a photosensitizer by developing a redox- and photo-responsive polymeric carrier system based on poly(lactic-<em>co</em>-glycolic acid) functionalized with cystamine and protoporphyrin IX, which could serve as a model for potential use in photodynamic therapy.</div><div>During the study, polymeric materials based on cystamine-protoporphyrin IX combination incorporated in poly(lactic-<em>co</em>-glycolic acid) were obtained, characterised in physicochemical studies and subjected to biological assessment. The presence of cystamine enabled the PPIX release in the presence of thiol triggers. The physicochemical characterisation of the new material was performed using UV–Vis, IR, NMR spectroscopies, X-Ray diffraction, and thermogravimetric analysis. The size and morphology of the obtained material were determined using nanoparticle tracking analysis, as well as SEM and TEM microscopy. The photochemical properties and stability of the material were analysed by establishing the singlet oxygen generation and photodecomposition quantum yields.</div><div>The acute toxicity of modified polymeric material was determined using the Microtox® test, whereas cyto- and photocytotoxicities were assessed <em>in vitro</em> on the human prostate cancer cell line (LNCaP) and human lung fibroblast (MRC-5). The polymer components, cystamine and PLGA, did not affect cell viability on their own, neither upon irradiation nor in the absence of light. The obtained polymeric material based on a protoporphyrin IX-cystamine molar ratio of 1:1 in PLGA could be considered a prospective formulation for PDT.</div><div>The novelty of our study lies in the design of a dual-responsive (redox and light) PLGA-based carrier system encapsulating protoporphyrin IX and a redox-cleavable linker, enabling controlled, photo-triggered release of the photosensitizer.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107209"},"PeriodicalIF":4.7000,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Pharmaceutical Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0928098725002088","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

By the use of suitable delivery systems and pharmaceutical formulations, improved transportation of photosensitizers to cancer cells in photodynamic therapy can be achieved. The aim of our study was to demonstrate controlled, redox-triggered release of a photosensitizer by developing a redox- and photo-responsive polymeric carrier system based on poly(lactic-co-glycolic acid) functionalized with cystamine and protoporphyrin IX, which could serve as a model for potential use in photodynamic therapy.

During the study, polymeric materials based on cystamine-protoporphyrin IX combination incorporated in poly(lactic-co-glycolic acid) were obtained, characterised in physicochemical studies and subjected to biological assessment. The presence of cystamine enabled the PPIX release in the presence of thiol triggers. The physicochemical characterisation of the new material was performed using UV–Vis, IR, NMR spectroscopies, X-Ray diffraction, and thermogravimetric analysis. The size and morphology of the obtained material were determined using nanoparticle tracking analysis, as well as SEM and TEM microscopy. The photochemical properties and stability of the material were analysed by establishing the singlet oxygen generation and photodecomposition quantum yields.

The acute toxicity of modified polymeric material was determined using the Microtox® test, whereas cyto- and photocytotoxicities were assessed in vitro on the human prostate cancer cell line (LNCaP) and human lung fibroblast (MRC-5). The polymer components, cystamine and PLGA, did not affect cell viability on their own, neither upon irradiation nor in the absence of light. The obtained polymeric material based on a protoporphyrin IX-cystamine molar ratio of 1:1 in PLGA could be considered a prospective formulation for PDT.

The novelty of our study lies in the design of a dual-responsive (redox and light) PLGA-based carrier system encapsulating protoporphyrin IX and a redox-cleavable linker, enabling controlled, photo-triggered release of the photosensitizer.

Abstract Image

查看原文本刊更多论文

基于半胱胺-原卟啉IX连接的聚合物材料在光动力治疗中的潜在应用-制备，物理化学性质和生物活性。

通过使用合适的输送系统和药物配方，可以实现光动力治疗中光敏剂向癌细胞的改善运输。我们研究的目的是通过开发一种基于聚乳酸-羟基乙酸-半胱胺和原卟啉IX功能化的氧化还原和光响应聚合物载体系统来证明光敏剂的可控氧化还原触发释放，该系统可以作为光动力治疗的潜在应用模型。在研究过程中，获得了基于半胺-原卟啉IX结合聚乳酸-共乙醇酸的聚合物材料，在物理化学研究中进行了表征，并进行了生物学评估。在巯基触发物存在的情况下，胱胺的存在使PPIX释放。新材料的物理化学特性是通过紫外可见，红外，核磁共振光谱，x射线衍射和热重分析进行的。采用动态光散射、扫描电镜和透射电镜对所得材料的尺寸和形貌进行了测定。通过建立单线态产氧和光分解量子产率，分析了材料的光化学性质和稳定性。使用Microtox®测试确定改性聚合物材料的急性毒性，而体外对人前列腺癌细胞系（LNCaP）和人肺成纤维细胞（MRC-5）的细胞和光细胞毒性进行评估。聚合物成分，胱胺和PLGA，本身不影响细胞活力，无论是在照射下还是在没有光的情况下。所获得的基于PLGA中原卟啉ix -半胺摩尔比为1:1的聚合物材料可以被认为是一种有前景的PDT配方。本研究的新颖之处在于设计了一种双响应（氧化还原和光）基于plga的载体系统，该系统封装了原卟啉IX和氧化还原可切割连接体，从而实现了光敏剂的可控光触发释放。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

European Journal of Pharmaceutical Sciences 医学-药学

CiteScore

9.60

自引率

2.20%

发文量

248

审稿时长

50 days

期刊介绍： The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.