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

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• The inflammatory microenvironment (IME) significantly influences triple-negative breast cancer (TNBC) progression.
• Baicalin (BA), an anti-inflammatory compound, has limited therapeutic potential in TNBC due to poor solubility and targeting.
• Developing effective drug delivery systems is crucial for modulating the IME in TNBC.

Purpose of the Study:

• To develop baicalin-loaded bifunctional albumin nanoparticles (BANP) for enhanced delivery and efficacy in TNBC.
• To investigate the physicochemical properties, pharmacokinetics, and tumor targeting of BANP.
• To evaluate the therapeutic effects of BANP on TNBC progression and the tumor immune microenvironment.

Main Methods:

• Synthesis and characterization of baicalin-loaded albumin nanoparticles (BANP) with core-shell structure.
• In vitro studies on cellular uptake, drug release kinetics, cell cycle arrest, and apoptosis induction in TNBC cells and macrophages.
• In vivo studies involving pharmacokinetic analysis, tumor accumulation, tumor growth inhibition in a TNBC mouse model, and analysis of tumor immune infiltration.
• Transcriptome sequencing and cytokine profiling to elucidate the mechanisms of IME modulation.

Main Results:

• BANP exhibited optimal particle size, zeta potential, and high encapsulation efficiency (72.71%).
• BANP demonstrated acid-sensitive release, enhanced cellular uptake by TNBC cells and M2 macrophages, prolonged circulation, and increased tumor accumulation.
• In vivo, BANP significantly inhibited tumor growth, reduced tumor immune infiltration, promoted M2 macrophage polarization, and enhanced M2 macrophage phagocytic activity.
• Transcriptome and cytokine analyses revealed that BANP regulate TNBC IME via multitarget mechanisms involving cell cycle, inflammation, and metabolism.

Conclusions:

• Bifunctional albumin nanoparticles (BANP) serve as an effective nanodelivery platform for baicalin in TNBC treatment.
• BANP demonstrate potential for modulating the tumor inflammatory microenvironment and enhancing anti-tumor immunity.
• This study presents a promising strategy for regulating IME and improving therapeutic outcomes in TNBC.