Silver nanoclusters show advantages in macrophage tracing in vivo and modulation of anti-tumor immuno-microenvironment.

Macrophage-based nanomedicine represents an emerging powerful strategy for cancer therapy. Unfortunately, some obstacles and challenges limit the translational applications of macrophage-mediated nanodrug delivery system. For instance, tracking and effective cell delivery for targeted tumor sites remain to be overcome, and controlling the states of macrophages is still rather difficult due to their plastic nature in response to external stimuli. To address these critical issues, here, we reported a novel type of silver nanoclusters (AgNCs) with excellent fluorescent intensity, especially long-lasting cell labeling stability after endocytosis by macrophages, indicating promising applications in tracking macrophage-based nanomedicine delivery. Our mechanistic investigations uncovered that these merits originate from the escape of AgNCs from lysosomal degradation within macrophages. In addition, the AgNCs would prime the M1-like polarization of macrophages (at least in part) through the toll-like receptor 4 signaling pathway. The engineered macrophages laden with AgNCs could be employed for lung metastasis breast cancer treatment, showing the effective targeting propensity to metastatic tumors, remarkable regulation of tumor immune microenvironment and inhibition of tumor growth. Collectively, AgNC-trained macrophages appear to be a promising strategy for tumor immune-microenvironment regulation, which might be generalized to a wider spectrum of cancer therapeutics.