Abstract

Metastatic melanoma (MM) is a skin malignancy arising from melanocytes, the incidence of which has been rising in recent years. It poses therapeutic challenges due to its resistance to chemotherapeutic drugs and radiation therapy. Photodynamic therapy (PDT) is an alternative non-invasive modality that requires a photosensitizer (PS), specific wavelength of light, and molecular oxygen. Several studies using conventional PSs have highlighted the need for improved PSs for PDT applications to achieve desired therapeutic outcomes. The incorporation of nanoparticles (NPs) and targeting moieties in PDT have appeared as a promising strategy to circumvent various drawbacks associated with non-specific toxicity, poor water solubility, and low bioavailability of the PSs at targeted tissues. Currently, most studies investigating new developments rely on two-dimensional (2-D) monocultures, which fail to accurately mimic tissue complexity. Therefore, three-dimensional (3-D) cell cultures are ideal models to resemble tumor tissue in terms of architectural and functional properties. This review examines various PS drugs, as well as passive and active targeted PS nanoparticle-mediated platforms for PDT treatment of MM on 2-D and 3-D models. The overall findings of this review concluded that very few PDT studies have been conducted within 3-D models using active PS nanoparticle-mediated platforms, and so require further investigation.

Highlights

  • Cancer refers to a variety of diseases caused by erratic proliferation of malignant cells, which can invade other parts of the body distant from the site of origin [1]

  • Allo and colleagues [113] reported that Photodynamic therapy (PDT) combined with the BRAF inhibitor vemurafenib resulted in significant tumor regression in a patient diagnosed with metastatic melanoma [113]

  • Metastatic melanoma remains a major health concern globally, and incidence rates have been on the rise in recent years [11]

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Summary

Introduction

Cancer refers to a variety of diseases caused by erratic proliferation of malignant cells, which can invade other parts of the body distant from the site of origin [1]. Treatments with target specificity for the oncogenic serine/threonine-protein kinase B-Raf (BRAF) proteins, which are universally expressed in melanoma cases, have shown a significant effect against MM [7] These therapies are hampered by drug resistance and adverse immunological reactions in patients [13]. The 3-D cell cultures integrating ECM materials, such as collagen, can serve as better cancer models in cancer research for the evaluation and testing of novel drugs since they resemble the fundamental aspects of the in vivo human cellular environment [19] Techniques, such as scaffolds, hanging drops, ultra-low attachment plates, micropatterned plates, spinner flasks, and microfluidic devices, are widely used for generating in vitro.

Photodynamic Therapy
PDT-Mediated Modes of Cell Death Induction
PSs Utilized in Metastatic Melanoma Treatment
Limitations of PDT in Metastatic Melanoma Treatment
Nanotechnology
Application of Nanotechnology in PDT Treatment
Passive PDT Nanoparticle-Mediated PS Delivery Platforms for MM Treatment
Active PDT Nanoparticle-Mediated PS Delivery Platforms for MM Treatment
Clinical Studies
Findings
Conclusions and Perspectives
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