Internalization-Responsive Nano-PLGA For Image-Guided Photodynamic Therapy Against HER2-Positive Breast Cancer

Abstract

Oncotheranostic nanoagents are powerful artificial compounds that significantly outperform traditional antitumor therapies. Among the wide variety of nanoagents, polymer nanoparticles have proven to be one of the most successful platforms for translation into the clinic. Here we show the development of an oncotheranostic nanoagent based on poly(lactic-co-glycolic acid) (PLGA) with red/green light dual-activated diagnostic/therapeutic properties for targeted photodynamic therapy of HER2-positive aggressive breast cancer. PLGA particles were loaded with red light-activated Nile Blue dye with pronounced solvatochromic properties for diagnostic applications and with green light-activated photodynamic sensitizer Rose Bengal for photodynamic therapy. The nanoparticles were decorated with anti-HER2 antibodies during the synthesis without chemical conjugation which is very important for further large-scale biotechnological production. In vitro and in vivo studies proved the red-light mediated HER2-specific imaging and green-light induced cytotoxicity of obtained anti-HER2 PLGA. Interestingly, these particles fluoresce only when internalized into cells, which minimizes background signals until the complete elimination from the organism, thus facilitating real-time diagnostics. We have shown that such particles allow efficient and selective localization of the HER2-positive primary tumor node, as well as metastases, and achieve complete remission in BALB/c Nu/Nu mice with the HER2-positive xenografts using the single session of photodynamic therapy.

Nanomedicine: Treatment of Chronic Disease Using Gold Nano Thermo Robot (GNTR) Empowered With Nanotechnology Approaches

“…Innovative heat-based medicines, particularly for the treatment of breast cancer, have been made possible by nanotechnology [26]. Hyperthermia (HT) is a clinical treatment for cancer that extraneously and intrinsically heats malignant cells to a temperature of 33𝐶 0 -45 𝐶 0 for suitable period [27].…”