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.

Surface Characteristics Affect the Properties of PLGA Nanoparticles as Photothermal Agents

“…Polymeric particles, specifically PLGA, are receiving significant attention among oncotheranostic agents due to their biocompatibility, non-toxic nature, and controlled drug-release properties [ 24 ]. PLGA nanoparticles can encapsulate a wide range of therapeutic agents, including drugs and imaging agents, protecting them from degradation and improving their stability and biodistribution [ 25 , 26 , 27 ]. Moreover, PLGA NPs can be easily customized through slight modifications in their synthesis parameters, which affect their size, surface charge, and composition.…”

“…PLGA NPs have applications across various fields of cancer treatment [ 19 , 26 , 27 , 28 , 29 ]—in particular, PLGA NPs are utilized as carriers in photothermal therapy. Photothermal therapy (PTT) is a non-invasive and highly selective method.…”

Targeted PLGA–Chitosan Nanoparticles for NIR-Triggered Phototherapy and Imaging of HER2-Positive Tumors

“…Nanoparticles were prepared by the double emulsion method, developed by us earlier, with modifications [ 39 , 40 , 41 , 42 ] ( Figure 1 ).…”

Nanoscale Ion-Exchange Materials: From Analytical Chemistry to Industrial and Biomedical Applications

“…Nonetheless, the proposed nanocarrier clearly requir ther development to accomplish targeted delivery. Its magnetization [85], e.g., by cating nanocomposite particles [9], modification with explicit moieties overexpres cancer cells [86], or noncovalent decoration with antibodies [87], might address th of enhancing tumor-specific uptake. The same NIE offers promise as a nanoplatform for the delivery of another fi chemotherapeutic agent, doxorubicin [36].…”