The Potential of Antibody Technology and Silver Nanoparticles for Enhancing Photodynamic Therapy for Melanoma

Abstract

Melanoma is highly aggressive and is known to be efficient at resisting drug-induced apoptotic signals. Resection is currently the gold standard for melanoma management, but it only offers local control of the early stage of the disease. Metastatic melanoma is prone to recurrence, and has a poor prognosis and treatment response. Thus, the need for advanced theranostic alternatives is evident. Photodynamic therapy has been increasingly studied for melanoma treatment; however, it relies on passive drug accumulation, leading to off-target effects. Nanoparticles enhance drug biodistribution, uptake and intra-tumoural concentration and can be functionalised with monoclonal antibodies that offer selective biorecognition. Antibody–drug conjugates reduce passive drug accumulation and off-target effects. Nonetheless, one limitation of monoclonal antibodies and antibody–drug conjugates is their lack of versatility, given cancer’s heterogeneity. Monoclonal antibodies suffer several additional limitations that make recombinant antibody fragments more desirable. SNAP-tag is a modified version of the human DNA-repair enzyme, O6-alkylguanine-DNA alkyltransferase. It reacts in an autocatalytic and covalent manner with benzylguanine-modified substrates, providing a simple protein labelling system. SNAP-tag can be genetically fused with antibody fragments, creating fusion proteins that can be easily labelled with benzylguanine-modified payloads for site-directed delivery. This review aims to highlight the benefits and limitations of the abovementioned approaches and to outline how their combination could enhance photodynamic therapy for melanoma.

Nanoparticle-Based Treatment Approaches for Skin Cancer: A Systematic Review

“…AgNPs exhibit high biocompatibility, resistance to oxidation, and a wide array of antimicrobial and anti-inflammatory activities [ 37 , 38 ]. AgNPs, when compared to AuNPs, have been found to have a greater photodynamic effect in PDT and generate more cytotoxic reactive oxygen species following irradiation, resulting in higher extinction coefficients in tumor cells, higher ratios of scattering to extinction, and higher field enhancement [ 37 ]. AgNPs, similarly to AuNPs, exhibit good optical absorbance and low toxicity towards normal cells, so they are a viable material for use in PTT as well [ 23 , 39 ].…”

Mutations in the Serine/Threonine Kinase BRAF: Oncogenic Drivers in Solid Tumors

“…There has also been some headway on incorporating theranostic treatment options, such as photodynamic therapy (PDT), into the arsenal of approaches that can be used to treat BRAF-mutant cancers [ 174 ]. PDT involves activating a photosensitizer with a specific wavelength of light, which then interacts with molecular oxygen to produce reactive oxygen species that kill targeted cells [ 175 ].…”

“…The specificity of PDT could prove to be useful in the treatment of BRAF-mutant cancers, especially in combination with other treatment strategies. Antibody–drug conjugates can also be used in the context of BRAFi resistance tumors to target specific antigens found on tumors, which help to reduce adverse effects in apoptosis-resistant histologies such as melanoma [ 174 ].…”

The fusion of light and immunity: Advancements in photoimmunotherapy for melanoma

“…Most notably, photosensitizing agents are being combined with a wide range of nanoparticle systems and/or conjugated to antibodies for better tumor specificity (reviewed in Ref. [37,31]). Next generation photosensitizing agents are also under constant development.…”