Tumor-associated macrophages (TAMs) generally display an immunosuppressive M2 phenotype and promote
tumor progression and
metastasis, suggesting their potential value as a target in
cancer immunotherapy.
Chlorogenic acid (CHA) has been identified as a potent
immunomodulator that promotes the polarization of TAMs from an M2 to an M1 phenotype. However, rapid clearance in vivo and low
tumor accumulation have compromised the immunotherapeutic efficacy of CHA in clinical trials. In this study, mannosylated
liposomes are developed for targeted delivery of CHA to TAMs. The immunoregulatory effects of CHA, along with the overall antitumor efficacy of CHA-encapsulated mannosylated
liposomes, are investigated through in vitro and in vivo experiments. The prepared CHA-encapsulated mannosylated
liposomes exhibit an ideal particle size, favorable stability, and preferential accumulation in
tumors via the
mannose receptor-mediated TAMs-targeting effects. Further, CHA-encapsulated mannosylated
liposomes inhibit G422
glioma tumor growth by efficiently promoting the polarization of the pro-tumorigenic M2 phenotype to the anti-tumorigenic M1 phenotype. Overall, these findings indicate that CHA-encapsulated mannosylated
liposomes have great potential to enhance the immunotherapeutic efficacy of CHA by inducing a shift from the M2 to the M1 phenotype.