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Abstract Biological neutralization represents a general strategy that deploys therapeutic agents to bind with harmful molecules or infectious pathogens, block their bioactivity, and thus prevent them from causing the diseases. Here, a comprehensive review of using cell‐membrane‐coated nanoparticles, namely “cellular nanosponges,” as host decoys for a wide range of biological neutralization applications is provided. Compared to traditional neutralization strategies, the cellular nanosponges stand out by mimicking susceptible host cells rather than accommodating the structures of the causative agents for the design of therapeutics. As all pathological agents must interact with host cells for bioactivity, nanosponges bypass the diversity of these agents and create function‐driven and broad‐spectrum neutralization solutions. The review focuses on the recent progress of using this new nanomedicine platform for neutralization against five primary pathological agents, including bacterial toxins, chemical toxicants, inflammatory cytokines, pathological antibodies, and viruses. Existing studies have established cellular nanosponges as versatile tools for biological neutralization. A thorough review of the cellular nanosponge technology is expected to inspire more refined cellular nanosponge designs and unique neutralization applications to address unsolved medical problems. 

Abstract White blood cells (WBCs) are immune cells that play essential roles in critical diseases including cancers, infections, and inflammatory disorders. Their dynamic and diverse functions have inspired the development of WBC membrane‐coated nanoparticles (denoted “WBC‐NPs”), which are formed by fusing the plasma membranes of WBCs, such as macrophages, neutrophils, T cells, and natural killer cells, onto synthetic nanoparticle cores. Inheriting the entire source cell antigens, WBC‐NPs act as source cell decoys and simulate their broad biointerfacing properties with intriguing therapeutic potentials. Herein, the recent development and medical applications of WBC‐NPs focusing on four areas, including WBC‐NPs as carriers for drug delivery, as countermeasures for biological neutralization, as nanovaccines for immune modulation, and as tools for the isolation of circulating tumor cells and fundamental research is reviewed. Overall, the recent development and studies of WBC‐NPs have established the platform as versatile nanotherapeutics and tools with broad medical application potentials.