Optimizing Dacarbazine Therapy: Design of a Laser-Triggered Delivery System Based on β-Cyclodextrin and Plasmonic Gold Nanoparticles

Dacarbazine (DB) is an antineoplastic drug extensively used in cancer therapy. However, present limitations on its performance are related to its low solubility, instability, and non-specificity. To overcome these drawbacks, DB was included in beta-cyclodextrin (beta CD), which increased its aqueous solubility and stability. This new beta CD@DB complex has been associated with plasmonic gold nanoparticles (AuNPs), and polyethylene glycol (PEG) has been added in the process to increase the colloidal stability and biocompatibility. Different techniques revealed that DB allows for a dynamic inclusion into beta CD, with an association constant of 80 M-1 and a degree of solubilization of 0.023, where beta CD showed a loading capacity of 16%. The partial exposure of the NH2 group in the included DB allows its interaction with AuNPs, with a loading efficiency of 99%. The PEG-AuNPs-beta CD@DB nanosystem exhibits an optical plasmonic absorption at 525 nm, a surface charge of -29 mV, and an average size of 12 nm. Finally, laser irradiation assays showed that DB can be released from this platform in a controlled manner over time, reaching a concentration of 56 mu g/mL (43% of the initially loaded amount), which, added to the previous data, validates its potential for drug delivery applications. Therefore, the novel nanosystem based on beta CD, AuNPs, and PEG is a promising candidate as a new nanocarrier for DB.