An antibody-conjugated polymer nanoparticle that targets inflammatory site for abdominal aortic aneurysm antioxidant...

Abdominal aortic aneurysm (AAA) tends to occur in the lower segment of the abdominal aorta in the elderly population. Its continuously growth and rupture risk seriously threaten the life and health of patients. AAA molecular pathomechanism is complex, its core mechanism is a IL-6 mediated immune response regulation and inflammatory mediators release, and b) oxidative stress triggered the programmed death of endothelial cells and vascular smooth muscle cells (VSMCs). Thereby, the damage to the blood vessel walls continues to worsen. The treatment of AAA with traditional drugs often has off-target effect and systemic toxicity. Surgical treatment also has many problems, such as large postoperative wound, significant complications and poor long-term efficacy. Therefore, this study developed an antibody-conjugated sustained-release nanoparticle, which loaded 2-MEthoxyestradiol (2ME) and target AAA inflammatory sites by significantly reducing mitochondrial oxidative stress damage in vascular endothelial cells through surface conjugation with tocilizumab (TCZ). The 2ME/TCZ modified nanomedicine (2MTNP) has long-term drug release ability, achieved oxidative stress inhibition in the AAA region and significantly restored the expression of mitochondrial anti-oxidative stress proteins PGC-1α, MT-CO1, and TFAM. In AAA mouse, the nanomedicine was highly enriched in areas of AAA, effectively slowing the expansion of AAA and the thinning of aortic vessel walls, thereby improving the survival of diseased mice. More importantly, PLGA-PEG nanocarrier-mediated drug delivery did not show significant organ toxicity such as liver and kidney in mice, demonstrating superior biocompatibility. This study reports an antibody-conjugated sustained-release nanodrug for targeted therapy of AAA, which provides a new treatment method for inflammatory vascular aneurysms.