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The Potential of Antibody Technology and Silver Nanoparticles for Enhancing Photodynamic Therapy for Melanoma
Zaria Malindi1, Stefan Barth2, Heidi Abrahamse1
1Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, 55 Beit Street, Doornfontein, Johannesburg 2028, South Africa.
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.
Insights
Advanced melanoma treatments are needed due to drug resistance. Combining photodynamic therapy with antibody-targeted nanoparticles and SNAP-tag technology offers improved drug delivery and melanoma treatment potential.
Area of Science:
- Oncology
- Biotechnology
- Nanomedicine
Background:
- Melanoma is an aggressive cancer with poor prognosis, necessitating novel therapeutic strategies beyond surgical resection.
- Current treatments face challenges including drug resistance, recurrence, and off-target effects, highlighting the need for advanced theranostic approaches.
- Photodynamic therapy (PDT) shows promise but is limited by passive drug accumulation and off-target toxicity.
Purpose of the Study:
- To review the limitations of current melanoma therapies and explore advanced theranostic alternatives.
- To evaluate the potential of combining photodynamic therapy with nanoparticle-based drug delivery systems.
- To assess the utility of SNAP-tag technology for targeted delivery in melanoma treatment.
Main Methods:
- Review of existing literature on melanoma treatment, photodynamic therapy, nanoparticles, antibody-drug conjugates, and SNAP-tag technology.
- Analysis of strategies to enhance drug biodistribution and intra-tumoral concentration using functionalized nanoparticles.
- Exploration of SNAP-tag's role in creating fusion proteins for site-directed payload delivery.
Main Results:
- Nanoparticles can improve drug delivery and concentration in tumors, while antibody conjugation offers targeted delivery.
- Antibody-drug conjugates reduce off-target effects but face limitations due to cancer heterogeneity.
- SNAP-tag technology, fused with antibody fragments, enables versatile, site-directed labeling for enhanced payload delivery.
Conclusions:
- Combining photodynamic therapy with antibody-targeted nanoparticles and SNAP-tag technology presents a promising strategy to overcome melanoma's therapeutic challenges.
- This integrated approach could significantly improve drug delivery, reduce off-target effects, and enhance treatment efficacy for metastatic melanoma.
- Further research into these combined modalities is crucial for developing next-generation melanoma theranostics.
