Advancements in nanomedicine for the therapeutic regulation of efferocytosis: opportunities and challenges.

Efferocytosis is a conserved event that plays an essential role in maintaining tissue homeostasis and immune balance. However, dysregulation of efferocytosis can induce disturbed apoptotic cells clearance and immune disorders, fueling an array of diseases, such as inflammatory diseases, autoimmunity, and cancers. The process of efferocytosis is dynamic and regulated by a complicated network composed of intracellular pathways and intercellular interactions, which pose significant challenges to current therapies. In recent years, nanomedicine-based strategies have shown potential in the precise regulation of efferocytosis for preventing or reversing pathology in diverse diseases. Although these results are encouraging, the opportunities and challenges in this field remain elusive and need to be comprehensively reviewed, which will be helpful for its improvement and future clinical translation. Here, we briefly introduce the key steps and signaling pathways of efferocytosis and its clinical relevance in diverse diseases. We highlight current advancements in nanomedicines for modulating efferocytosis, especially their design principles and therapeutic applications across a broad range of diseases, such as chronic inflammation, cardiovascular diseases, autoimmune diseases, neurodegenerative diseases and cancers. We discuss the ongoing clinical trials and discuss the challenges and limitations in this field, which may provide insights into developing precision nanomedicines to modulate efferocytosis for treating diverse forms of diseases.