Tannic\nAcid-Based Biomimetic Nanomedicine with Pathological\nReactive Oxygen Species-Responsive Cargo Release for Relieving Inflammation\nin Rheumatoid Arthritis

Rheumatoid\narthritis (RA) is a chronic disease characterized by\nimmune cell infiltration and cartilage damage. The local lesion of\nRA shows severe oxidative stress and proinflammatory cytokine secretion.\nFor drug therapy, the efficacy of agents, such as methotrexate (MTX),\nmay be greatly limited, resulting from the low bioavailability, immune\nclearance, and toxic side effects. A nanocarrier (TA-PBA NPs) was\ndeveloped with anti-inflammatory and antioxidant activities, combined\nwith MTX to prepare nanomedicine (MTX NPs) for synergistic treatment\nof RA. Moreover, inspired by the biological functions homing to inflammation\nlesion of macrophages, the biomimetic nanomedicine camouflaged with\nmacrophage membrane (MM@MTX NPs) was constructed. TA-PBA NPs could\ntimely promote MTX release in response to the overaccumulated ROS\nto exhibit high anti-inflammatory and antioxidant activities for alleviating\nRA progression. The experimental results confirmed that MM@MTX NPs\ncould significantly reduce the secretion of proinflammatory cytokines\n(TNF-α) while significantly increasing the typical anti-inflammatory\ncytokines (IL-10), promote the phenotype transformation of macrophages\nfrom M1 to M2, and up-regulate the Nrf2-keap1 pathway-related proteins\n(HO-1 and NRF2) to positively regulate the local inflammation for\neffectively inhibiting RA development. Thus, MM@MTX NPs represent\na possible candidate as a safe and efficient nanotherapy platform\nfor RA management.