Perspectives on the application of nanotechnology in photodynamic therapy for the treatment of melanoma

Abstract

Malignant melanoma is the most aggressive form of skin cancer and has been traditionally considered difficult to treat. The worldwide incidence of melanoma has been increasing faster than any other type of cancer. Early detection, surgery, and adjuvant therapy enable improved outcomes; nonetheless, the prognosis of metastatic melanoma remains poor. Several therapies have been investigated for the treatment of melanoma; however, current treatment options for patients with metastatic disease are limited and non-curative in the majority of cases. Photodynamic therapy (PDT) has been proposed as a promising minimally invasive therapeutic procedure that employs three essential elements to induce cell death: a photosensitizer, light of a specific wavelength, and molecular oxygen. However, classical PDT has shown some drawbacks that limit its clinical application. In view of this, the use of nanotechnology has been considered since it provides many tools that can be applied to PDT to circumvent these limitations and bring new perspectives for the application of this therapy for different types of diseases. On that ground, this review focuses on the potential use of developing nanotechnologies able to bring significant benefits for anticancer PDT, aiming to reach higher efficacy and safety for patients with malignant melanoma.

Keywords: melanoma; nanoparticles; nanotechnology; photodynamic therapy; skin cancer.

Fig. 1

Diagram illustrating the main events leading to photoreactions of type I and II that ultimately may lead to oxidative cell damage. PS=photosensitizer; ¹PS*=singlet excited state PS; ³PS*=triplet excited state PS; hν=photon; ISC=intersystem crossing; ³O₂=triplet oxygen; ¹O₂=singlet oxygen; S=substrates (biomolecules); S_mod=chemically modified biomolecules.

Fig. 2

Contribution of different compounds to the optical density of biological tissues.

Fig. 3

An ideal multifunctional nanosystem for the treatment of melanoma using photodynamic therapy (PDT), hyperthermia, site specific drug delivery, and targeting moieties. Photosensitizers and chemotherapeutics can be coupled or encapsulated to a silica or polyacrylamide shell for simultaneous PDT/chemotherapeutic treatment with site specific drug delivery. Nanoparticles can also be targeted to cells of interest or to tumor vasculature by surface-functionalization with targeting molecules. Contrast enhancers can also be incorporated as diagnostic agents.