Nano-baicalein facilitates chemotherapy in breast cancer by targeting tumor microenvironment.

Cancer-associated fibroblasts constitute a significant component in the tumor microenvironment, playing a pivotal role in tumor proliferation, invasion, migration, and metastasis. Consequently, therapy combining chemotherapeutic agents with tumor microenvironment (TME) modulators appears to be a promising avenue for cancer treatment. In this paper, a tumor microenvironment-based mPEG-PLGA nanoparticle loaded with baicalein (PMs-Ba) was constructed for the purpose of improving the tumor microenvironment in cases of triple-negative breast cancer. The results demonstrate that, on the one hand, PMs-Ba was able to inhibit the transforming growth factor β(TGF-β) signaling pathway to avoid the activation of cancer-associated fibroblasts (CAFs), thereby influencing the interstitial microenvironment of the tumor. On the other hand, the agent led to an increase in the infiltration of cytotoxic T cells, activating the tumor immune microenvironment. Meanwhile, in the murine breast cancer model, an intravenous injection of PMs-Ba combined with doxorubicin nanoparticles (PMs-ADM) significantly improved the antitumor effectiveness. These results suggest that baicalein encapsulated in nanoparticles may be a promising strategy for modulating the TME and for adjuvant chemotherapy, signifying a potential TME-remodeling nanoformulation that could enhance the antitumor efficacy of nanotherapeutics.