Micro/Nanoparticles in the Nose-Brain Axis: Implications for Pathogenesis and Therapeutic Interventions

Ya-Kui Mou,1– 4,* Quan Li,2,5,* Yao Wang,1– 4,* Xiao-Yu Song,1– 4 Han-Rui Wang,1– 4 Wan-Chen Liu,1– 4 Yuan-Chao Cheng,1– 4 Hui Shen,1– 4 Chao Ren,2,6,7 Xi-Cheng Song1– 4 1Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 2Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China; 3Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China; 4Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 5Department of Emergency, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 6Department of Neurology, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 7Yantai Municipal Key Medical and Health Laboratory of Yantai Yuhuangding Hospital (Interdisciplinary Brain Science and Geriatric Health Laboratory), Qingdao University, Yantai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao Ren, Department of Neurology. Yantai Yuhuangding Hospital, Qingdao University, No. 20, East Road, Zhifu District, Yantai, 264000, People’s Republic of China, Tel +86535 6691999, Fax +86535 6240341, Email [email protected] Xi-Cheng Song, Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, No. 20, East Road, Zhifu District, Yantai, 264000, People’s Republic of China, Tel +86535 6691999, Fax +86535 6240341, Email [email protected]: The nose-brain axis (NBA) is a crucial bidirectional deliverypathway between the nasal cavity and the central nervous system (CNS) that influences both neurophysiology and disease progression. In addition to serving as a route for drug delivery, the NBA plays an active role in neurological disorders by mediating inflammatory responses, microbial interactions, and environmental exposure. Emerging evidence suggests that the NBA may be mechanistically relevant to CNS disorders, particularly within neurodegeneration frameworks such as the Braak and dual-hit hypotheses, which emphasize early olfactory or other peripheral involvements. This review explores how micro/nanoparticles interact with the NBA, not only as therapeutic carriers but also as factors contributing to neuroinflammation and neurodegeneration. Pathogenic micro/nanoparticles, including environmental pollutants and industrial nanoparticles, have been implicated in the exacerbation of CNS disorders by triggering oxidative stress and immune activation in both nasal and brain tissues. Conversely, therapeutic micro/nanoparticles such as biomimetic, synthetic, and cell-derived formulations represent promising strategies for modulating neuroinflammation, enhancing neuroprotection, and restoring CNS function through nasal-targeted interventions. However, substantial gaps remain in the existing understanding of the influences of nasal immune responses, microbiota, and barrier integrity on CNS health through the NBA. Addressing these challenges is critical for leveraging micro-/nanoparticles for the prevention and treatment of CNS diseases. Keywords: nose-brain axis, micro/nanoparticles, neuroinflammation, neurodegenerative diseases