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2Optimizing photothermal therapy for melanoma: the role of peptide-coated gold nanorods and laser irradiation parameters
LMikhailova1*, E. Vysotina1, M. Zyuzin1
1- School of Physics and Engineering, ITMO University, St. Petersburg 191002, Russian Federation
Melanoma is a type of skin cancer characterised by the uncontrolled growth of melanocytes, which are cells that produce the pigment melanin. It is one of the most aggressive forms of skin cancer, and its incidence is increasing worldwide [1]. Current treatments for melanoma include surgery, chemotherapy, and immunotherapy; however, these treatments often have significant side effects and may not be effective for all patients [2,3]. Targeted therapy is a promising approach for the treatment of melanoma. This approach uses affine molecules specifically designed to target and destroy cancer cells [4]. These molecules can be used to modify nanoparticles or complexes bringing therapeutic properties. Gold nanorods (Au NRs) are a type of agent for targeted therapy that is effective for treating various types of cancer because of their ability to heat under laser irradiation, which can provoke cell death [5]. Since melanoma metastasises very rapidly and aggressively, targeted photothermal therapy is an excellent treatment option. It allows targeted agents to be delivered to tumour sites and effectively affect them.
This study presents a novel approach to melanoma therapy using gold nanorods (Au NRs) modified with two distinct melanoma-targeted peptides and evaluated under femtosecond (FS) and nanosecond (NS) pulsed laser irradiation regimes. The Au NRs were coated with Ac-12, which closely mimics the a-melanocyte-stimulating hormone (aMSH) sequence, and GKR, which targets melanocortin receptors (MC1R) and includes additional linkers for enhanced conjugation. The peptide-coated Au NRs were extensively characterised and tested in vitro and in vivo for their targeting ability, heating efficiency, and therapeutic efficacy.
Au NRs were synthesised and coated with Ac-12 or GKR peptides using a ligand exchange procedure. Cellular uptake, melanogenesis, and cell viability studies were conducted using B16-F10 melanoma cells. In vivo studies used C57BL/6 mice injected with B16-F10 cells to model melanoma. Photoacoustic imaging was used to assess tumour targeting, and histological analysis was performed to determine the safety of Au NRs. Photothermal therapy (PTT) was performed using FS (1030 nm, 1400 mW/cm2) and NS (1064 nm, 1400 mW/cm2) laser irradiation for 3 min.
In vitro studies showed that both Au@Ac-12 and Au@GKR effectively targeted and internalised into melanoma cells, causing concentration-dependent receptor-mediated melanogenesis. FS laser irradiation resulted in a more distinct temperature distribution profile and induced more intense tumour ablation than NS laser irradiation. In vivo photoacoustic imaging revealed that Au@Ac-12, with its higher affinity to MC1R, accumulated in tumours at a higher rate than Au@GKR. FS laser irradiation led to a significant decrease in tumour volume, particularly when applied shortly after Au NR injection. Histological analysis confirmed the safety of intravenously and intratumorally injected Au NRs, with no inflammatory reactions or cytotoxicity effects observed in the major organs.
This study demonstrates the potential of targeted melanoma therapy using peptide-coated Au NRs and differential laser irradiation. The Ac-12 peptide, with its higher affinity to MC1R, and the FS laser irradiation regime, with its enhanced heating capabilities, showed the most promising results in terms of tumour targeting and destruction.
[1] Five-Year Survival Rates | SEER Training, (n.d.). https://training.seer.cancer.gov/melanoma/intro/survival.html (accessed May 7, 2024).
[2] B. Katta, C. Vijayakumar, S. Dutta, The Incidence and Severity of Patient-Reported Side Effects of Chemotherapy in Routine Clinical Care: A Prospective Observational Study, Cureus, vol. 15,4 e38301, (2023).
[3] H. Majeed, V. Gupta, Adverse Effects of Radiation Therapy, StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK563259/.
[4] B. Yin, W. Ho, X. Xia, A Multilayered Mesoporous Gold Nanoarchitecture for Ultraeffective Near-Infrared Light-Controlled Chemo/Photothermal Therapy for Cancer Guided by SERS Imaging, Small, 19, 6, (2023).
[5] H. Kong, J. Han, M. Yang, Two-dimensional peptide nanosheets functionalized with gold nanorods for photothermal therapy of tumors, Journal of Materials Chemistry B, 11, 3445-3452, (2023).
