Author(s): Lidia Mikhailova, Elizaveta Vysotina, Maria Timofeeva, Elena Kopoleva, Van Gulinyan, Olesia Pashina, Konstantin Arabuli, Olga Gusliakova, Ekaterina Prikhozhdenko, Xiaoli Qi, Andrey Petrov, Eduard Ageev, Mihail Petrov, Constantino De Angelis, Mikhail Durymanov, Gleb Sukhorukov, Mikhail V. ZyuzinLidia Mikhailova, Elizaveta Vysotina, Maria Timofeeva, Elena Kopoleva, Van Gulinyan, Olesia Pashina, Konstantin Arabuli, Olga Gusliakova, Ekaterina Prikhozhdenko, Xiaoli Qi, Andrey Petrov, Eduard Ageev, Mihail Petrov, Constantino De Angelis, Mikhail Durymanov, Gleb Sukhorukov, Mikhail V. Zyuzin
ABSTRACT
Melanoma, a highly malignant and complex form of cancer, has increased in global incidence, with a growing number of new cases annually. Active targeting strategies, such as leveraging the α-melanocyte-stimulating hormone (αMSH) and its interaction with the melanocortin 1 receptor (MC1R) overexpressed in melanoma cells, enhance the concentration of therapeutic agents at tumor sites. For instance, targeted delivery of plasmonic light-sensitive agents and precise hyperthermia management provide an effective, minimally invasive treatment for tumors. In this work, we present a comparative study on targeted photothermal therapy (PTT) using plasmonic gold nanorods (Au NRs) as a robust and safe nanotool to reveal how key treatment parameters affect therapy outcomes. Using an animal model (B16-F10) of melanoma tumors, we compare the targeting abilities of Au NRs modified with two different MC1R agonists, either closely mimicking the αMSH sequence or providing a superior functionalization extent of Au NRs (4.5% (w/w) versus 1.8% (w/w)), revealing 1.6 times better intratumoral localization. Following theoretical and experimental assessments of the heating capabilities of the developed Au NRs under laser irradiation in either the femtosecond (FS)- or nanosecond (NS)- pulsed regime, we perform targeted PTT employing two types of peptide-modified Au NRs and compare therapeutic outcomes revealing the most appropriate PTT conditions. Our investigation reveals greater heat release from Au NRs under irradiation with FS laser, due to the relaxation rates of the electron and phonon temperatures dissipating in the surrounding, which correlates with a more pronounced 17.6 times inhibition of tumor growth when using FS-pulsed regime.