Natural Cell-Inspired Nanoparticles: Preparation, Mechanisms, Applications, and Prospects for Clinical Translation.

Natural cell-inspired nanoparticles (NCINPs) represent a transformative innovation in nanomedicine, featuring a core-shell structure coated with isolated natural cell membranes (NCMs) that effectively mimic the functions of native cells. The development of NCINPs achieves molecular-level emulation of native cells by precisely reconstructing the hierarchical architecture of the bio-interface, including the structure of the phospholipid bilayer, lipid rafts, protein matrix, and polysaccharide interactions. This advanced biomimetic strategy not only retains the inherent biocompatibility and targeting precision of natural cells but also enables programmable functionalities that surpass those of natural systems, offering enhanced therapeutic potential. In this review, an in-depth introduction to the background of natural cell-inspired research is provided, the current prevalent synthesis methods of NCINPs is delineated, and the application mechanisms based on various types of NCMs, as well as their applications in both benign and malignant diseases are elucidated. However, clinical translation faces significant challenges: complex synthesis, compromised membrane functionality, and unpredictable in vivo behavior. The work comprehensively synthesizes the progress, limitations, and challenges encountered throughout the development of NCINPs, while delineating future prospects. Bridging the translational gap from bench to bedside accelerates the clinical translation of NCINPs and fully realizes their therapeutic potential across diverse medical applications.