Photothermal efficiency of indocyanine green J-aggregates by nanoformulation with calix[4]arene
Résumé
Photothermal therapy (PTT) is an emerging approach in cancer therapy due to minimal invasiveness, and because it appears as a promising extension of photodynamic therapy since it does not require oxygen to interact with cells, as PTT is based on temperature increase inside cancer cells to induce cell death.
Indocyanine green (ICG) is a fluorescent contrast agent approved by the United States Food and Drug Administration (FDA) for angiography in ophthalmology, in sentinel lymph node biopsy and detection of metastasis. The good absorption properties of ICG make it also ideal for PTT applications in the near infrared (NIR) region, allowing deep tissue penetration. However, its PTT efficacy is restricted by intrinsic limitations including rapid photodegradation, instability in solution correlated with rapid clearance from the body (2-4min in circulation). These limitations led to the use of nanosized ICG-J aggregates (ICGJ).
ICG-J aggregates are characterized by a 105 nm redshifted absorption (from 785 nm to 890 nm), a severe diminution of fluorescence and a better photothermal efficiency. Unfortunately, ICG-J quickly disassemble in the presence of plasma proteins that limits its in vivo efficiency.
In our study, we utilized amphiphilic tetracationic calix[4]arene (CX) to engineered ICG-J/CX by nanoprecipitation with ICG-J, a strategy inspired by the work from Yasuda et al. in 2016, who highlighted an improvement in the stability and in optical properties of ICG when combined with calixarenes.
Our ICG-J/CX nanoprecipitation, which could be easily and quickly prepared and possess close to neutral charge and a size around 130 nm, demonstrated high photothermal capacities, decrease photobleaching than that observed for free ICG or ICG-J, and excellent stability in
biological medium. In vitro, on monolayer human pharyngeal adenocarcinoma cells (FaDu), these properties have led to improved cellular uptake, absence of dark cytotoxicity, and considerable decrease of the ICG concentration required to reach high photothermal therapeutic effect compared to simple ICG or ICG-J. Thus, our nanoprecipitation demonstrates a high potential for PTT and open up new avenues for attaining cancer treatment.