Design of nanoformulation of specialized pro-resolving mediators to facilitate inflammation resolution and disease treatment

Inflammation is a strong defense mechanism the body uses to fight against microbial infection and tissue damage. However, uncontrolled acute inflammation would develop into chronic inflammation, leading to diseases including cancer and tissue fibrosis as well as damage to tissues and organs. Specialized pro-resolving mediators (SPMs) enzymatically generated from omega-3 or omega-6 long-chain polyunsaturated fatty acids are effective in moderating resolving and non-resolving inflammation, such as reducing organ and tissue injuries, chronic conditions, tissue fibrosis, and relieving COVID-19, at low pM concentrations. However, the molecular processes underpinning SPM actions have yet to be completely understood. For therapeutic purposes, there are also some drawbacks to using SPMs for disease treatment, including rapid enzymatic breakdown, low targeting efficiency, high cost, and safety issues with long-term systemic administration. The advancement of nanoformulation has paved the way to address these issues. In this review, to develop the nanoformulation of SPMs, we detailed the discovery, synthesis, metabolism, and cell-type-specific actions of SPMs to gain a better understanding of their character traits. We also outline the molecular pathways involved in SPMs-mediated disease treatment. The fundamental understanding of SPM biology serves as the basis for designing SPMs-based (or derived) nanomedicine, enabling the effective management of various pathological processes where the inflammation resolution mechanisms play essential roles with drugable potential. This makes SPM biomedical applications to be more widely available, efficient, controlled, multi-functional, and precise.