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

Oncotheranostic nanoagents are powerful artificial toolsthat significantly outperform traditional antitumor therapies. Amongthe wide variety of nanoagents, poly(lactic-co-glycolic acid) (PLGA)nanoparticles have proven to be one of the most successful candidatesfor translation into clinical practice. Here, we present PLGA nanoparticlesfor HER2-targeted diagnostic and photodynamic therapy with provenefficacy in vivo. Namely, we developed an oncotheranostic platformthat is based on PLGA nanoparticles and possesses red/green lightdual-activated diagnostic/therapeutic properties for HER2-targetedphotodynamic therapy of aggressive breast cancer. PLGA nanoparticleswere loaded with a red light-activated dye Nile Blue with pronouncedsolvatochromic properties for diagnostic applications and with a greenlight-activated photodynamic sensitizer Rose Bengal for photodynamictherapy. Targeted delivery was ensured by the noncovalent decorationof nanoparticles with anti-HER2 antibodies, which can be readily adaptedfor large-scale biotechnological production. In vitro and in vivostudies proved the effectiveness of red light-mediated HER2-specificimaging and green light-induced cytotoxicity of anti-HER2 PLGA. Interestingly,these particles fluoresced only after cellular internalization, whichminimizes background signals inside the organism, thus facilitatingreal-time diagnostics. The particles allowed efficient and selectivevisualization of the HER2-positive primary tumor node and metastasesspread and led to complete remission in BALB/c Nu/Nu mice with theHER2-positive xenografts after a single session of photodynamic therapy.