Drug-Loaded Three-Dimensional Scaffolds: A Promising Strategy for Targeted Skin Cancer Therapy

Drug-Loaded Three-Dimensional Scaffolds: A Promising Strategy for Targeted Skin Cancer Therapy
Ana Mousazadeh,¹ Vahid Asghariazar,^2,*
1. Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
2. Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
Introduction: Three-dimensional (3D) scaffolds have recently emerged as a promising and innovative strategy in cancer therapy. Unlike conventional two-dimensional (2D) culture systems, which have long been used to study tumor biology and evaluate anticancer drugs, 3D scaffolds better mimic the native tumor microenvironment. This structural resemblance enables a more accurate assessment of cancer cell behavior, proliferation, and response to therapeutic agents. While 2D models have provided valuable insights, they are limited by their inability to reproduce the three-dimensional architecture of tumor tissues, lack of complex cell–cell and cell–matrix interactions, and differences in drug diffusion and penetration compared with in vivo conditions. Consequently, findings derived from 2D models are often not fully translatable to clinical practice. Loading drugs into 3D scaffolds offers new opportunities for skin cancer therapy by enabling controlled and targeted delivery of chemotherapeutics, natural compounds, or nanocarriers directly to the tumor site. Multiple loading strategies, including physical adsorption, covalent bonding, and nanoparticle encapsulation, have been developed to enhance drug stability, improve bioavailability, and regulate release kinetics. Evidence from melanoma and non-melanoma skin cancer models suggests that drug-loaded scaffolds provide sustained drug release, reduce systemic toxicity, and significantly improve therapeutic efficacy. Additionally, scaffolds enable the co-delivery of multiple therapeutic agents or the combination of drug delivery with gene therapy, which is critical in overcoming drug resistance. Key advantages of this approach include targeted and localized drug delivery, reduced adverse effects, enhanced biocompatibility, and potential for patient-specific customization. However, challenges remain, such as limited scalability, heterogeneity in scaffold architecture, and the translational gap between preclinical studies and clinical applications. Future directions will likely focus on developing innovative and personalized scaffolds capable of responding to environmental stimuli (e.g., pH, enzymatic activity, or temperature) and regulating drug release with spatial and temporal precision.
Methods: Method: This review summarizes findings from recent studies retrieved from PubMed and Scopus using the keywords: 3D scaffolds, Drug delivery, Skin cancer, Biomaterials, and Nanotechnology.
Results: Results: Current evidence demonstrates that drug-loaded 3D scaffolds enhance local drug retention, minimize systemic toxicity, and improve therapeutic outcomes in skin cancer models.
Conclusion: Drug-loaded 3D scaffolds represent a novel and practical approach for skin cancer therapy, bridging biomaterials engineering and oncology. Despite encouraging preclinical evidence, further research is necessary to address translational challenges, optimize scaffold design, and validate clinical efficacy. Integrating nanotechnology, immunotherapy, and personalized scaffold engineering holds great potential to transform future cancer management strategies.
Keywords: 3D scaffolds, Drug delivery, Skin cancer, Biomaterials, Nanotechnology