Nanotechnology Addressing Cutaneous Melanoma: The Italian Landscape

Abstract

Cutaneous melanoma is one of the most aggressive solid tumors, with a low survival for the metastatic stage. Currently, clinical melanoma treatments include surgery, chemotherapy, targeted therapy, immunotherapy and radiotherapy. Of note, innovative therapeutic regimens concern the administration of multitarget drugs in tandem, in order to improve therapeutic efficacy. However, also, if this drug combination is clinically relevant, the patient’s response is not yet optimal. In this scenario, nanotechnology-based delivery systems can play a crucial role in the clinical treatment of advanced melanoma. In fact, their nano-features enable targeted drug delivery at a cellular level by overcoming biological barriers. Various nanomedicines have been proposed for the treatment of cutaneous melanoma, and a relevant number of them are undergoing clinical trials. In Italy, researchers are focusing on the pharmaceutical development of nanoformulations for malignant melanoma therapy. The present review reports an overview of the main melanoma-addressed nanomedicines currently under study in Italy, alongside the state of the art of melanoma therapy. Moreover, the latest Italian advances concerning the pre-clinical evaluation of nanomedicines for melanoma are described.

Melanoma and Nanotechnology-Based Treatment

“…To improve the efficacy of drugs, various new multitarget drugs are often used in combination in the clinical setting. Nanotechnology-based DDSs, such as nanoliposomes, can play key roles in the clinical treatment of advanced melanoma because nanomaterials can target drug delivery at the cellular level by overcoming biological barriers in the body ( 32 , 36 , 37 ).…”

“…For example, liposomes, solid lipid nanoparticles, and nanoemulsions have been developed as lipid nanosystems, whereas silica nanoparticles, gold nanoparticles, copper nanoparticles, and nanotubes have been used as common inorganic nanoparticle systems. Polymerization systems include polymeric micelles, nanospheres, polymeric nanoparticles, hydrogels, and dendritic macromolecules, and exosomes are a type of natural nanosystem ( 36 ).…”

Ultrasound-Responsive Nrf2-Targeting siRNA-Loaded Nanobubbles for Enhancing the Treatment of Melanoma

“…Metastatic melanoma (MM) is poorly responsive to treatment based on conventional chemotherapy, resulting in a 5-year survival rate of only 15% [2]. Over the past few years, new targeted treatments and immunotherapy [3,4] have significantly improved the global approach toward melanoma. Activating mutations in cytoplasmic serine/threonine kinase B-Raf (BRAF), belonging to the mitogen-activated protein kinase (MAPK) signaling pathway, are the most frequent genetic alterations present in approximately 50% of all melanoma cases [5].…”

Parenteral Nanoemulsions Loaded with Combined Immuno- and Chemo-Therapy for Melanoma Treatment

“…In stage IIB/C (tumor thickness > 2.0 mm) and stage III, adjuvant chemotherapies are practiced following surgery. Dacarbazine, the standard chemotherapy for stage IV (metastatic) melanoma up to 2011, is simply a palliative care treatment [ 1 ]. Temozolomide (TMZ) is an alternative treatment as it can reach the central nervous system (CNS) to treat brain metastases [ 2 ].…”

“…Since half of the total melanomas show the V-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation, they may respond to targeted therapies with BRAF (vemurafenib, dabrafenib, encorafenib) and/or mitogen-activated protein kinase (MEK) inhibitors (trametinib, cobimetinib, binimetinib). Moreover, melanomas respond to immunotherapy with monoclonal antibodies that block the immune checkpoint receptors cytotoxic T-lymphocyte antigen 4 (CTLA4), such as ipilimumab, and programmed cell death protein 1 (PD1), such as pembrolizumab and nivolumab [ 1 ]. Indeed, melanoma is one of the most immunogenic tumors and its relationship with the host immune system is currently under investigation [ 3 ].…”