Development of functional nanomedicines for tumor associated macrophages-focused cancer immunotherapy.

Clinical cancer immunotherapies are usually impeded by tumor immunosuppression driven by tumor associated macrophages (TAMs). Thus, TAMs can be considered as a promising therapeutic target for improved immunotherapy, and TAMs-focused molecular targeting agents have made ideal progress in clinical practice. Even so, most TAMs-targeting agents still cannot cover up their own shortcomings as free drugs. The emergence of multifunctional nanomaterials can expectedly endow these therapeutic cargoes with high solubility, favorable pharmacokinetic distribution, cell-specific delivery, and controlled release. Here, the underlying mechanisms of tumor immunosuppression caused by TAMs are first emphatically elucidated, and then the basic design of TAMs-focused immune-nanomedicines are discussed, mainly including diverse categories of nanomaterials, targeted and stimulus-responsive modifications, and TAM imaging in nanomedicines. A summary of current TAMs-targeting immunotherapeutic mechanisms based on functional nanomedicines for TAMs elimination and/or repolarization is further presented. Lastly, some severe challenges related to functional nanomedicines for TAMs-focused cancer immunotherapy are proposed, and some feasible perspectives on clinical translation of TAMs-associated anticancer immunonanomedicines are provided. It is hoped that, with rapid development of nanomedicine in cancer immunotherapy, TAMs-focused therapeutic strategies may be anticipated to become an emerging immunotherapeutic modality for future clinical cancer treatment.