Natural polyphenol-loaded cross-linked lipoic acid vesicles treat triple-negative breast cancer by cancer cell killing and metastasis inhibition

Abstract

The high incidence of metastases remains a major hurdle for triple negative breast cancer (TNBC) treatment. Herein, we developed a fairly safe anticancer nanodrug for TNBC treatment by loading Epigallocatechin-3-gallate (EGCG) in cross-linked lipoic acid vesicles (EGCG@cLAVs), which cannot only directly kill TNBC cells through inducing apoptosis, but also significantly suppress the TNBC metastasis by metalloproteinases (MMPs) inhibition, a key event in tumor extracellular matrix (ECM) remodeling. The cytotoxicity assay revealed that the ICEGCG50 of EGCG@cLAVs (85.1 μM) fell in the range of common cytotoxic drugs. The in vitro antimetastasis results disclosed that the EGCG@cLAVs effectively suppressed the migration and invasion of TNBC cells (4T1) with low wound healing rate and relative invasion rate of 19.10 ± 2.12% and 15.0 ± 1.63%, 4.0 and 6.7 times lower than that of control, respectively. The outcomes of animal models revealed that EGCG@cLAVs not only achieved the comparable antitumor effect to that of first-line chemotherapeutic drug DOX, but also reduced the number of lung metastatic nodules from 31.4 (DOX) to 1.4. This nanodrug provides a promising candidate for TNBC therapy.