LAUSR

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.