BODIPY-Based NO Probe for Macrophage-Targeted Immunotherapy Response Monitoring.

Precise and rapid detection of immune responses is critical for timely therapeutic regimen adjustment. Immunomodulation of tumor-associated macrophages (TAMs) from a protumorigenic phenotype (M2) to an antitumorigenic phenotype (M1) is crucial in macrophage-targeted immunotherapy. Herein, we developed a boron dipyrromethene (BODIPY)-based fluorescence probe BDP3 to detect the immune responses after immunotherapy by monitoring the nitric oxide (NO) released by M1 TAMs. With an aromatic primary monoamine structure and a p -methoxyanilin electron donor in the meso -position, BDP3 not only specifically activates stable and sensitive fluorescence by NO via a photoinduced electron transfer (PET) process but also achieves a long emission wavelength for efficient in vitro and in vivo imaging. Such NO-induced fluorescence signals of BDP3 are validated to correlate well with the phenotypes of TAMs detected in macrophage cell lines and tumor tissues. The distinct sensing effects toward two types of clinically used immunotherapeutic drugs further confirm the ability of BDP3 for specific monitoring of the M1/M2 switch in response to the macrophage-targeted immunotherapy. By virtue of good biocompatibility and appropriate tumor retention time, BDP3 could be a potential fluorescent probe for noninvasive evaluation of the immunotherapeutic efficacy of macrophage-targeted immunotherapy in living animals.