State Key Laboratory of Solidification Processing, Center of Advanced Lubrication and Seal Materials, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi'an 710072, PR China.
School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi'an 710021, PR China.
J Colloid Interface Sci. 2025 Feb;679(Pt B):788-797. doi: 10.1016/j.jcis.2024.10.162. Epub 2024 Oct 28.
Developing stimulus-responsive properties of drug delivery nanocarriers combined with enhanced joint lubrication is an effective synergistic strategy for treating osteoarthritis. Poly(N-isopropylacrylamide) (PNIPAm) is a typical thermo-responsive polymer, which can achieve drug delivery by transition from swollen state to collapsed state. However, undesired transition temperature, limited drug loading capacity, and weakened mechanical properties in joint present obstacles to use as drug delivery nanocarriers. In this work, we demonstrate dose-effect relationship between the PNIPAm-based copolymer and nanoscale metal-organic frameworks on enhancing both aqueous lubrication and drug delivery performance of a hybrid osteoarthritis (OA) nanocarrier. A series of NIPAm and poly(ethylene glycol)methacrylate (PEGMa) copolymer microgels with different feeding content are optimized to grow on the surface of MIL-101(Cr) nanoparticles via one-pot soap-free emulsion copolymerization method. By changing the feeding mass ratio of NIPAm and PEGMa, MIL-101(Cr)@P(NIPAm-g-PEGMa) (x = 0, 1, 2, 3, and 4, named MPNP) hybrids can ameliorate the lower critical solution temperature to match with OA and enhance the aqueous lubrication performance. Among the as-synthesized hybrids, MPNP hybrids manifested the notable enhanced thermo-responsive tribological performance due to the synergistic effect of "hydration lubrication" and "ball-bearing" function of the optimized copolymer microgel layer on the surface of metal-organic frameworks (MOFs). Anti-inflammatory drug loading is enabled by the high surface area and porosity of the MOFs, and the MPNP drug delivery nanocarriers achieve thermo-responsive release in vitro. Our work establishes the dose-effect relationship between thermo-responsive NIPAm and hydrophilic PEGMa of the copolymer grown on the surface of MOFs, providing valuable insights for improving the versatility of stimuli-responsive for biomedical application.
开发具有刺激响应特性的药物输送纳米载体并结合增强关节润滑是治疗骨关节炎的一种有效协同策略。聚（N-异丙基丙烯酰胺）（PNIPAm）是一种典型的温敏聚合物，可通过从溶胀状态转变为塌陷状态来实现药物输送。然而，不理想的转变温度、有限的药物载量和关节中减弱的机械性能成为其作为药物输送纳米载体的障碍。在这项工作中，我们展示了基于 PNIPAm 的共聚物与纳米级金属有机骨架之间的剂量效应关系，以增强混合骨关节炎（OA）纳米载体的水润滑和药物输送性能。通过一锅无皂乳液共聚方法，优化了一系列具有不同进料含量的 NIPAm 和聚（乙二醇）甲基丙烯酸酯（PEGMa）共聚物微凝胶，以在 MIL-101（Cr）纳米粒子表面生长。通过改变 NIPAm 和 PEGMa 的进料质量比，可以改善 MIL-101（Cr）@P（NIPAm-g-PEGMa）（x=0、1、2、3 和 4，分别命名为 MPNP）杂化物的较低临界溶液温度以与 OA 相匹配，并提高水润滑性能。在所合成的杂化物中，由于优化的共聚微凝胶层在金属-有机骨架（MOFs）表面上的“水合润滑”和“滚珠轴承”功能的协同作用，MPNP 杂化物表现出显著增强的温敏摩擦学性能。MOFs 的高表面积和孔隙率使抗炎药物负载成为可能，并且 MPNP 药物输送纳米载体在体外实现了温敏释放。我们的工作建立了在 MOFs 表面生长的共聚物中温敏的 NIPAm 和亲水性 PEGMa 之间的剂量效应关系，为提高刺激响应在生物医学应用中的多功能性提供了有价值的见解。
