Baicalin-Loaded Bifunctional Albumin Nanoparticles Inhibit Triple-Negative Breast Cancer Growth by Remodeling the Inflammatory Microenvironment.

Abstract

The inflammatory microenvironment (IME) is closely related to the progression of triple-negative breast cancer (TNBC). As an anti-inflammatory active compound, poor solubility and targeting limit the potential of baicalin (BA) to modulate IME in TNBC. In this study, BA loaded bifunctional albumin nanoparticles (BANP) with long circulation/acid-sensitive release and active targeting functions are developed to improve the delivery efficiency of BA. BANP have a spherical core-shell structure, with appropriate particle size (79.63 ± 1.91 nm), zeta potential (-33.7 ± 0.82 mV), and encapsulation efficiency (72.71%), and are released faster in an acidic environment. BANP can enhance the uptake by TNBC cells and "M2" macrophages, prolong circulation time in the blood, and increase accumulation at tumor sites in vivo. It induces cell cycle arrest and early apoptosis in MDA-MB-231 cells and inhibits tumor growth in 4T1 tumor-bearing mice. Additionally, BANP reduce tumor immune infiltration, promote macrophage recruitment and anti-inflammatory M2 polarization, and enhance the phagocytic activity of M2 macrophages. Transcriptome sequencing and cytokine profile analysis reveal that BANP regulate TNBC IME through multitarget mechanisms related to cell cycle, inflammatory response, metabolism, etc. In summary, this study provides a nanodelivery platform with broad application potential and a new strategy for the regulation of IME.