EV Surface Engineering Enables Cell-Specific Targeting for Immune Modulation in Inflammatory Diseases

Extracellular vesicles (EVs) hold significant promise as natural nanocarriers for immune modulation in inflammatory diseases due to their biocompatibility and cargo transport capabilities. However, their clinical translation is hampered by limited cell-specific targeting and uncontrolled biodistribution. Achieving precise delivery to specific immune cells and inflammation-associated components within diseased tissues is crucial for maximizing therapeutic efficacy and minimizing off-target effects. This review addresses this critical gap by summarizing strategies for enhanced EV targeting.

This comprehensive review synthesizes recent advances in developing cell-specific EV-targeting strategies for immune modulation in inflammatory diseases. The authors focused on active targeting approaches, specifically those enabled by EV surface engineering. They discussed a wide array of targeting ligands, including antibodies, peptides, aptamers, glycans, and membrane proteins, examining their roles in enhancing selective interactions between EVs and specific immune cell subsets. Special emphasis was placed on strategies for directing EVs toward diverse immune cell populations, such as macrophages and T cells, to reprogram immune phenotypes and suppress pathological inflammation.

The review identified that EV surface engineering with various targeting ligands significantly enhances selective interactions with specific immune cell subsets. Discussed ligands included antibodies, peptides, aptamers, glycans, and membrane proteins, each offering distinct advantages for directing EVs. These strategies enable precise targeting of diverse immune cell populations, notably macrophages and T cells, which are critical players in inflammatory responses. The authors highlighted how such targeted delivery can be leveraged to reprogram immune phenotypes, effectively suppress pathological inflammation, and restore immune homeostasis. This rational control over EV-cell interactions is presented as a key to unlocking the therapeutic potential of EVs.

Rational control of EV-cell interactions can be utilized to reprogram immune phenotypes, suppress pathological inflammation, and restore immune homeostasis.