Degradable Theranostic Polyurethane for Macrophage-Targeted Antileishmanial Drug Delivery.

IF 5.5 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomacromolecules Pub Date : 2025-02-10 Epub Date: 2025-01-03 DOI:10.1021/acs.biomac.4c01273

Sagar Bag, Arunava Seth, Desoshree Ghosh, Rupak Datta, Priyadarsi De

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Abstract

The present investigation aims to develop a reactive oxygen species (ROS) and esterase-responsive biodegradable mannosylated polyurethane to effectively deliver the encapsulated antileishmanial drug amphotericin B (AmB) selectively to infected macrophage cells. Owing to suitable amphiphilic balance, the as-synthesized glycosylated polyurethane (PU2M) with aryl boronic ester-based diol (M2) moiety as ROS-trigger, water-soluble mannose pendants, and fluorescent 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) chain ends for bioimaging formed nanoaggregates in an aqueous medium as confirmed by ¹H NMR spectroscopy, dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and critical aggregation concentration (CAC) measurements. Aided by two endogenous stimuli present in phagolysosome, ROS and esterase, AmB-encapsulated polymeric nanoaggregates as drug delivery vehicles achieved an efficient reduction of both L. donovani and L. major intracellular amastigote burden compared to the free AmB. Overall, this work illustrated a promising therapeutic application of dual endogenous stimuli-triggered degradable theranostic polyurethane for target-specific drug delivery of AmB, to mitigate leishmaniasis.

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巨噬细胞靶向抗利什曼原虫药物递送的可降解治疗性聚氨酯。

本研究旨在开发一种活性氧（ROS）和酯酶反应的可生物降解甘露糖基化聚氨酯，以有效地将包封的抗利什曼原虫药物两性霉素B （AmB）选择性地递送到感染的巨噬细胞。通过1H NMR波谱、动态光散射（DLS）、场发射扫描电子显微镜（FESEM）、透射电子显微镜（TEM）等方法证实，合成的以芳基硼酯基二醇（M2）片段为ros触发器、水溶性甘露糖悬垂和用于生物成像的荧光4,4-二氟-4-硼-3a，4 -二氮-s-茚二烯（BODIPY）链末端的糖基化聚氨酯（PU2M）在水介质中形成纳米聚体。临界聚集浓度（CAC）测量。在吞噬溶酶体（ROS）和酯酶两种内源性刺激的帮助下，与游离AmB相比，AmB封装的聚合物纳米聚集体作为药物递送载体，有效地减少了L. donovani和L. major胞内无马鞭毛菌的负担。总的来说，这项工作说明了双内源性刺激触发的可降解治疗性聚氨酯用于靶向药物递送AmB，以减轻利什曼病的治疗应用前景广阔。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.