Nanomaterials for Skin Cancer Photoimmunotherapy

Abstract

Skin cancer is one of the most common types of cancer, and its incidence continues to increase. It is divided into two main categories, melanoma and non-melanoma. Treatments include surgery, radiation therapy, and chemotherapy. The relatively high mortality in melanoma and the existing recurrence rates, both for melanoma and non-melanoma, create the need for studying and developing new approaches for skin cancer management. Recent studies have focused on immunotherapy, photodynamic therapy, photothermal therapy, and photoimmunotherapy. Photoimmunotherapy has gained much attention due to its excellent potential outcomes. It combines the advantages of photodynamic and/or photothermal therapy with a systemic immune response, making it ideal for metastatic cancer. This review critically discusses different new nanomaterials' properties and mechanisms of action for skin cancer photoimmunotherapy and the main results obtained in the field.

Keywords: basal cell carcinoma; immunotherapy; melanoma; photodynamic therapy; photothermal therapy; squamous cell carcinoma.

Figure 1

Nanomaterial types used for skin cancer photoimmunotherapy. The main categories are metallic, polymeric, lipid-based, and 2D nanoparticles. Created with BioRender.com.

Figure 2

Surface functionalization strategies used for skin cancer photoimmunotherapy. Functionalization with PEG (polyethylene glycol), polysaccharides, lipids, polymers, aptamers, peptides, and antibodies. Created in Biorender.com. Abbreviations: HA, hyaluronic acid; PVP, poly-(vinylpyrrolidone); PVA, Polyvinyl alcohol. Created with BioRender.com.

Figure 3

Skin cancer photoimmunotherapy using functionalized nanoparticles. The nanoparticles can exert a direct effect on cells by destroying primary tumors and activating immune cells. Photoimmunotherapy can induce an inflammatory response and increase the release of pro-inflammatory cytokines (e.g., TNF-α, IFN-γ, IL-6, IL-12). Nanoparticles were modified using specific drugs, polymers, or antibodies to induce a desired immune response. Abbreviations: TSAs, tumor-specific antigens; DAMPs, damage-associated molecular patterns; IL-6, interleukin-6; IL-12, interleukin-12; TNF-α, tumor necrosis factor alpha; INF-γ, interferon gamma. Created with BioRender.com.

Figure 4

Examples of skin cancer photo-immunotherapeutic modulation using nanomaterials. (A) BSA-bioinspired gold nanorods (GNRs) decorated with PEG and loaded with R837 administered to B16F10 tumor-bearing mice followed by NIR laser irradiation (1064 nm, 1.0 W cm⁻², 10 min), mPEG-GNRs@BSA/R837 + Laser group; (a) Cytokine levels of TNF-α, IL-6, and IL-12 in the serum of mice 3 days after various treatments; (b) Cytokine secretion of TNF-α from macrophages stimulated by treated B16-F10 tumor after various treatments; (c) Weight of primary tumor 15 days after various treatments. * p < 0.05, ** p < 0.01, *** p < 0.001. Used with permission of Royal Society of Chemistry, from [97]; permission conveyed through Copyright Clearance Center, Inc. (B) PDMAEMA polycation on the outside of SiO₂ surface integrated with the plasmid encoding IL-12 gene (1064 nm, 0.65 W cm⁻², 5 min), CSP@IL-12 + Laser group; (a) Average weights of the excised tumors after different treatments as indicated (* p < 0.05, ** p < 0.01, *** p < 0.001, compared to the PBS group; # p < 0.05, ## p < 0.01, pairwise comparison; n = 5); (b) The percentages of CD80+/CD86+ DC cells in the tumor-draining lymph nodes (gated on CD11c+).; (c) The percentages of CD3+/CD4+ T cells in the spleen; (d) The percentages of CD3+/CD8+ T cells. (* p < 0.05, ** p < 0.01, *** p < 0.001, compared to the PBS group; # p < 0.05, ## p < 0.01, pairwise comparison; n = 3). Data are presented as mean ± SD. Used with permission of Royal Society of Chemistry, from [108]; permission conveyed through Copyright Clearance Center, Inc.

Figure 5

In vivo studies on skin cancer photo-immunomodulation effects induced by nanomaterials. (A) Imiquimod encapsulated in amphiphilic peptide-based micelles (IQPM) applied to B16F10 tumor-bearing mice together with NIR laser irradiation (808 nm, 1.5 W cm⁻¹, 5 min); (a) Photographs of lung tissues taken 21 days after treatments; (b) Quantification of average number of tumor nodules in lung tissues (n = 4, one-way ANOVA and Student–Newman–Keuls test, * p < 0.05; *** p < 0.001); (c) IFN-𝛾 secretion from splenocytes of treated mice (n = 3, one-way ANOVA and Student–Newman–Keuls test, *** p < 0.001). Reproduced with permission from [103] © 2023 Wiley-VCH GmbH. (B) PPP/CpG/HA nanoplatform applied to B16-F10 tumor mice model together with laser irradiation (808 nm, 1.5 W cm⁻², 5 min); (a) Weight of isolated tumors after treatment (mean ± SD, n = 5); (b) Frequency of infiltrating CD8+ T cells in tumor; (c) infiltrating CD8+ T cells in spleens. ∗∗, and ∗∗∗ indicate p < 0.05, p < 0.01 and p < 0.001, respectively. Reprinted from [107], Copyright @ 2023, with permission from Elsevier.