Porphyrin-Polymer as a Photosensitizer Prodrug for Antimicrobial Photodynamic Therapy and Biomolecule Binding Ability.

IF 5.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomacromolecules Pub Date : 2024-11-08 DOI:10.1021/acs.biomac.4c01011

Leila Tabrizi, Ross McGarry, Kaja Turzanska, Lazaros Varvarezos, Muireann Fallon, Ruairi Brannigan, John T Costello, Deirdre Fitzgerald-Hughes, Mary T Pryce

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Abstract

This study presents the development and characterization of a novel porphyrin-Jeffamine polymer conjugate designed to function as a photosensitizer prodrug for antimicrobial photodynamic therapy (aPDT). The conjugate features a photosensitive porphyrin unit covalently attached to a biocompatible polymer backbone, with enhanced solubility, stability, and bioavailability compared to those of the free porphyrin derivatives. The photophysical properties were studied using transient absorption spectroscopy spanning the fs-μs time scales in addition to emission studies. The production of reactive oxygen species upon photoactivation enabled effective bacterial cell killing. Spectroscopic studies confirmed strong binding of the conjugate to DNA through intercalation, likely disrupting DNA replication and transcription. Interaction studies with bovine serum albumin demonstrated substantial serum protein binding, which may positively impact the pharmacokinetics and biodistribution. Overall, this porphyrin-polymer conjugate offers a multifunctional theranostic platform, combining antimicrobial action with DNA and protein binding potential, positioning it as a promising candidate for aPDT and bioimaging applications.

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卟啉-聚合物作为光敏剂原药用于抗菌光动力疗法和生物大分子结合能力。

本研究介绍了一种新型卟啉-Jeffamine 聚合物共轭物的开发和表征，该共轭物可作为光敏剂原药用于抗菌光动力疗法（aPDT）。该共轭物的特点是光敏卟啉单元共价连接到生物相容性聚合物骨架上，与游离卟啉衍生物相比，其溶解性、稳定性和生物利用度都有所提高。除了发射研究外，还利用跨越 fs-μs 时间尺度的瞬态吸收光谱对光物理性质进行了研究。光激活后产生的活性氧能有效杀死细菌细胞。光谱研究证实，共轭物通过插层作用与 DNA 紧密结合，很可能会破坏 DNA 复制和转录。与牛血清白蛋白的相互作用研究表明，卟啉与大量血清蛋白结合，这可能会对药代动力学和生物分布产生积极影响。总之，这种卟啉-聚合物共轭物提供了一个多功能治疗平台，将抗菌作用与 DNA 和蛋白质结合潜力结合在一起，使其成为一种很有希望应用于 aPDT 和生物成像的候选物质。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.