Department of Chemical Engineering, University of Mississippi, University, MS, 38677, USA.
Department of Biomedical Engineering, University of Mississippi, University, MS, 38677, USA.
Macromol Biosci. 2022 Dec;22(12):e2200281. doi: 10.1002/mabi.202200281. Epub 2022 Sep 28.
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.
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受到全身非靶向毒性的影响，导致治疗窗口非常狭窄。为了解决这一缺点，开发了一种基于聚（丙烯基硫化物）-b-聚（甲基丙烯酰胺基吡喃葡萄糖）[PPS-b-PMAG]两亲嵌段共聚物的纳米粒子（PMAG NPs），能够靶向巨噬细胞并在活性氧（ROS）存在的情况下释放药物。PMAG NPs 具有系统药物输送的理想物理化学性质，包括略负的表面电荷、约 100nm 的直径和血液相容性。此外，由于 NP 核中存在 PPS，PMAG NPs 优先在 ROS 存在的情况下释放药物货物。重要的是，PMAG NPs 显示出高细胞相容性，并以比 PEGMA NPs-NPs（由 PPS-b-聚（聚乙二醇甲基丙烯酸酯）组成）高约 18 倍的速率被巨噬细胞摄取。计算研究表明，PMAG NPs 可能与巨噬细胞膜表面上的葡萄糖转运蛋白（如 GLUT1/3）结合，从而促进高水平的内化。总的来说，这项研究介绍了糖基聚合物 NPs，它们具有独特的受体配体靶向巨噬细胞和 ROS 依赖性药物释放的能力，在许多免疫治疗环境中可能具有应用价值。
