<br>ROS响应性糖聚合物纳米颗粒可增强巨噬细胞的药物输送,Macromolecular Bioscience

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ROS响应性糖聚合物纳米颗粒可增强巨噬细胞的药物输送
Macromolecular Bioscience ( IF 4.4 ) Pub Date : 2022-09-20 , DOI: 10.1002/mabi.202200281
Oluwaseyi T Shofolawe-Bakare ₁ , Judith U de Mel ₂ , Sushil K Mishra ₃ , Mehjabeen Hossain ₃ , Christine M Hamadani ₄ , Mercedes C Pride ₄ , Gaya S Dasanayake ₄ , Wake Monroe ₄ , Eric W Roth ₅ , Eden E L Tanner ₄ , Robert J Doerksen ₃ , Adam E Smith _{1,

2} , Thomas A Werfel _{1,

2,

3,

6}

Affiliation

巨噬细胞在许多病理学中发挥着多样化的关键作用，包括炎症性疾病、心血管疾病和癌症。然而，许多针对巨噬细胞的治疗策略都存在全身性脱靶毒性，导致治疗窗口极其狭窄。为了解决这一缺点，开发了基于聚（丙烯硫醚） -b-聚（甲基丙烯酰胺吡喃葡萄糖）[PPS -b -PMAG]二嵌段共聚物的纳米颗粒（PMAG NP），该纳米颗粒能够靶向巨噬细胞并在活性氧存在的情况下释放药物（ROS）报告。 PMAG NP 具有适合全身药物输送的理想物理化学特性，包括轻微的负表面电荷、直径约 100 nm 和血液相容性。此外，由于 NP 核心中存在 PPS，PMAG NP 在 ROS 存在的情况下优先释放药物。重要的是，PMAG NP 显示出高细胞相容性，并且在细胞培养物中被巨噬细胞吸收的速度比 PEGMA NP（由 PPS- b-聚（低聚乙二醇甲基丙烯酸酯）组成的 NP）高约 18 倍。计算研究表明，PMAG NP 可能与巨噬细胞表面的 GLUT 1/3 等葡萄糖转运蛋白结合，以促进高水平的内化。总的来说，这项研究引入了糖聚合物纳米颗粒，它们具有独特的受体配体靶向巨噬细胞和 ROS 依赖性药物释放能力，可用于许多免疫治疗环境。

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ROS-Responsive Glycopolymeric Nanoparticles for Enhanced Drug Delivery to Macrophages

Macrophages play a diverse, key role in many pathologies, including inflammatory diseases, cardiovascular diseases, and cancer. However, many therapeutic strategies targeting macrophages suffer from systemic off-target toxicity resulting in notoriously narrow therapeutic windows. To address this shortcoming, the development of poly(propylene sulfide)-b-poly(methacrylamidoglucopyranose) [PPS-b-PMAG] diblock copolymer-based nanoparticles (PMAG NPs) capable of targeting macrophages and releasing drug in the presence of reactive oxygen species (ROS) is reported. PMAG NPs have desirable physicochemical properties for systemic drug delivery, including slightly negative surface charge, ≈100 nm diameter, and hemo-compatibility. Additionally, due to the presence of PPS in the NP core, PMAG NPs release drug cargo preferentially in the presence of ROS. Importantly, PMAG NPs display high cytocompatibility and are taken up by macrophages in cell culture at a rate ≈18-fold higher than PEGMA NPs—NPs composed of PPS-b-poly(oligoethylene glycol methacrylate). Computational studies indicate that PMAG NPs likely bind with glucose transporters such as GLUT 1/3 on the macrophage cell surface to facilitate high levels of internalization. Collectively, this study introduces glycopolymeric NPs that are uniquely capable of both receptor-ligand targeting to macrophages and ROS-dependent drug release and that can be useful in many immunotherapeutic settings.

更新日期：2022-09-20

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