Internalization-Responsive Poly(lactic-co-glycolic acid) Nanoparticles for Image-Guided Photodynamic Therapy against HER2-Positive Breast Cancer

Abstract

Oncotheranostic nanoagents are powerful artificial tools that significantly outperform traditional antitumor therapies. Among the wide variety of nanoagents, poly(lactic-co-glycolic acid) (PLGA) nanoparticles have proven to be one of the most successful candidates for translation into clinical practice. Here, we present PLGA nanoparticles for HER2-targeted diagnostic and photodynamic therapy with proven efficacy in vivo. Namely, we developed an oncotheranostic platform that is based on PLGA nanoparticles and possesses red/green light dual-activated diagnostic/therapeutic properties for HER2-targeted photodynamic therapy of aggressive breast cancer. PLGA nanoparticles were loaded with a red light-activated dye Nile Blue with pronounced solvatochromic properties for diagnostic applications and with a green light-activated photodynamic sensitizer Rose Bengal for photodynamic therapy. Targeted delivery was ensured by the noncovalent decoration of nanoparticles with anti-HER2 antibodies, which can be readily adapted for large-scale biotechnological production. In vitro and in vivo studies proved the effectiveness of red light-mediated HER2-specific imaging and green light-induced cytotoxicity of anti-HER2 PLGA. Interestingly, these particles fluoresced only after cellular internalization, which minimizes background signals inside the organism, thus facilitating real-time diagnostics. The particles allowed efficient and selective visualization of the HER2-positive primary tumor node and metastases spread and led to complete remission in BALB/c Nu/Nu mice with the HER2-positive xenografts after a single session of photodynamic therapy.