Traditional Chinese medicine (TCM) enhances the therapeutic efficiency of a gemcitabine-loaded injectable hydrogel on postoperative breast cancer through modulating the microenvironment

Abstract

Local injection of the drug-loaded hydrogel at the surgery site is promising for postoperative breast cancer. However, the postoperative changes in the tumor microenvironment, such as inflammation, abnormal angiogenesis and hypoxia, inhibit drug perfusion and contribute to breast cancer recurrence (BCR). Normalizing the abnormal blood vessels can effectively improve perfusion and reduce hypoxia. Here, we encapsulated gemcitabine (GEM) in a PLGA–PEG–PLGA hydrogel (GEM-hydrogel) for local treatment of postoperative breast cancer. The GEM-hydrogel can be injected into the surgery cavity allowing sustained release of the drug. Meanwhile, traditional Chinese medicine (TCM) Shexiang Baoxin Pill (SBP) was given to normalize the blood vessels to enhance drug perfusion. The results suggest that the combination of SBP enhances the therapeutic efficiency of the GEM-hydrogel, inhibiting tumor recurrence. Mechanism studies reveal that SBP works by promoting PDGFB expression in macrophages, subsequently recruiting pericytes, and normalizing blood vessels, finally alleviating hypoxia. This study demonstrates that the combination of TCM and chemotherapeutics is promising for suppressing postoperative tumor recurrence.