Internalization-Responsive Nano-PLGA 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, polymer nanoparticles have proven to be one of the most successful candidates for translation into clinical practice. Here we developed an oncotheranostic platform that is based on poly(lactic-co-glycolic acid) nanoparticles and possesses red/green light dual-activated diagnostic/therapeutic properties for targeted photodynamic therapy of HER2-positive 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 non-covalent 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.