Tailored hyaluronic acid-based nanogels as theranostic boron delivery systems for boron neutron cancer therapy

• Main Authors: Simon Coninx (Author), Ghadir Kalot (Author), Amélie Godard (Author), Ewen Bodio (Author), Christine Goze (Author), Lucie Sancey (Author), Rachel Auzély-Velty (Author)
• Format: Book
• Published: Elsevier, 2022-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2590-1567; 10.1016/j.ijpx.2022.100134
• Keywords: Nanogel; Hyaluronic acid; Boron neutron capture therapy; Aza-BODIPY; Theranostic; Boron compound; Pharmacy and materia medica; RS1-441
• Source: International Journal of Pharmaceutics: X, Vol 4, Iss , Pp 100134- (2022)

Boron-rich nanocarriers possess great potential for advanced boron neutron capture therapy (BNCT) as an effective radiation treatment for invasive malignant tumors. If additionally, they can be imaged in a non-invasive and real-time manner allowing the assessment of local boron concentration, they could serve for dose calculation and image-guided BNCT to enhance tumor treatment efficacy. To meet this challenge, this study describes the design of a theranostic nanogel, enriched in 10B and fluorescent dye, to achieve selective imaging, and sufficient accumulation of boron at the tumor site. The boron-rich and fluorescent nanogels can be easily obtained via temperature triggered-assembly of hyaluronic acid (HA) modified with a thermoresponsive terpolymer. The latter was specifically designed to enable the efficient encapsulation of the fluorescent dye - an aza‑boron-dipyrromethene (aza-BODIPY) - linked to 10B-enriched sodium borocaptate (BSH), in addition to induce nanogel formation below room temperature, and to enable their core-crosslinking by hydrazone bond formation. The HA nanogel considerably concentrates aza-BODIPY-BSH into the hydrophobic nanodomains made of the terpolymer chains. Here, we present the detailed synthesis of the HA-terpolymer conjugate, nanogel formation, and characterization in terms of size, morphology, and stability upon storage, as well as the biological behavior of the boron nanocarrier using real-time fluorescence imaging in cells and in vivo. This work suggested the potential of the theranostic HA nanogel as a boron delivery system for the implementation of BNCT in brain cancer and sarcoma.