Abstract
Photodynamic therapy (PDT) has been pointed out as a candidate for improving melanoma treatment. Nanotechnology application in PDT has increased its efficacy by reducing side effects. Herein, mesoporous silica nanoparticles (MSNs) conjugated with verteporfin (Ver-MSNs), in use with PDT, were administered in mice to evaluate their efficacy on lymphoangiogenesis and micrometastasis in melanoma. Melanoma was induced in mice by the subcutaneous injection of B16-F10 cells. The mice were transcutaneously treated with MSNs, Ver-MSNs, or glycerol and exposed to red light. The treatment was carried out four times until day 20. Lymphangiogenesis and micrometastasis were identified by the immunohistochemical method. Lymphoangiogenesis was halved by MSN treatment compared with the control animals, whereas the Ver-MSN treatment almost abolished it. A similar reduction was also observed in lung micrometastasis. PDT with topically administrated Ver-MSNs reduced melanoma lymphoangiogenesis and lung micrometastasis, as well as tumor mass and angiogenesis, and therefore their use could be an innovative and useful tool in melanoma clinical therapy.
Highlights
Cancer spread or metastasis is the most important predictor of patient prognosis, so the main effort to address a cancer form is to study and counter the spread of cancer cells [1].It is widely known that most cancers spread their metastases through the lymphatic vessels that drain liquids and cells from the tissue microenvironment
One active melanoma dissemination strategy is lymphangiogenesis [6,7], as confirmed by the work of Lund et al [8], where spontaneous lung metastasis from primary melanomas was decreased in a mouse strain lacking dermal lymphatic vessels
Our group already used Ver conjugated with mesoporous silica nanoparticles (MSNs) [17,19] (Figure 1) to topically treat mouse melanoma obtaining both tumor angiogenesis and mass reduction [20]. In this part of an in vivo study, we evaluated the efficacy of photodynamic therapy with verteporfin-loaded mesoporous silica nanoparticles to reduce tumor lymphoangiogenesis and affect micrometastasis
Summary
Clinical studies have indicated that lymphatic vessels may be colonized by hosting small nodules of tumoral cells, having the potential to disseminate secondary tumors over a long period of time [3,4]. This may give the lymphatic vessels a critical role in the tumor dissemination process. Cutaneous melanoma (CM) is a highly metastatic tumor characterized by rapid systemic dissemination [5]. One active melanoma dissemination strategy is lymphangiogenesis (the formation of lymphatic vessels associated with tumor growth) [6,7], as confirmed by the work of Lund et al [8], where spontaneous lung metastasis from primary melanomas was decreased in a mouse strain lacking dermal lymphatic vessels
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