Table 5.

In vitro and in vivo assessment of the therapeutic potential of different metallic-based nanoparticles in melanoma models.

Nanosystem Composition	Compound(s)	Model(s)	Summary of Experimental Assays and Conditions	Main Conclusions	Reference
MoO3 NPs	Non-applicable	In vitro: human G361 cell line	Cell viability assay: MTT (50–400 μg/μL)	MoO3 NPs showed selective cytotoxicity against malignant skin cells compared to healthy cells.	[165]
AgPt NPs	Non-applicable	In vitro: human A375 cell line	Cell viability assays: MTS (10–250 µg/mL)	NPs demonstrated antitumor activity in the A375 cell line while being safe for healthy cells.	[166]
Pd NPs	Non-applicable	In vitro: human A375 cell line	Cell viability assays (0–40 μg/mL): MTT and NRU DNA damage assays: comet, cell cycle arrest (EtBr) ROS detection assay: H2DCFDA oxidative stress detection assay: BCA Cell death assays: DAPI, AO/EtBr and caspase-3 activity	In vitro assays demonstrated cytotoxic and genotoxic activity of Pd NPs on melanoma cells.	[169]
Cu NPs	Non-applicable	In vitro: human A375 cell line	Cell viability assay: MTT (up to 4.5 μg/mL) Cell membrane fluidity assay: TMA-DPH DNA damage assays: comet (EtBr), chromosomal condensation (DAPI) and cell cycle arrest (PI) ROS detection assay: H2DCFDA Mitochondrial membrane potential assay: JC-1 Cell death assays: annexin V-FITC/PI and caspase-3 activity	Cu NPs promoted DNA damage, cell cycle arrest in the G2/M phase and depolarization of mitochondrial membrane potential.	[170]
Cu2O NPs	Non-applicable	In vitro: murine B16F10 cell line	Cell viability assay: MTT (2.5, 5 and 10 μg/mL) ROS detection assay: H2DCFDA Mitochondrial membrane potential assay: JC-1 Cell death assays: annexin V-FITC/PI and caspase-3 and caspase-9 activities	Cu2O NPs reduced selectively cancer cell lines viability in vitro. Similarly, in an in vivo context, a significant anti-tumor efficacy, impaired tumor growth progression and inhibition of lung metastasis was observed.	[171]
		In vivo: subcutaneous and metastatic models; male C57BL/6 mice; s.c. and i.v. injection of B16F10 cells, respectively	i.v. and i.t. administration of Cu2O NPs in subcutaneous (16 mg/kg) and metastatic (2 mg/kg) model, respectively
Au NPs	DOX	In vitro: murine B16 and human SK-MEL-28 cell lines	Cell viability assay: SRB	Au-DOX was efficiently internalized and demonstrated great cytotoxicity in melanoma cells. In vivo assays also demonstrated its sustained inhibition of tumor progression over time when compared to DOX alone.	[172]
		In vivo: male C57BL/6 mice; s.c. injection of B16 cells and female nude mice, s.c. injection of SKMEL-28 cells	Administration of free DOX, Au NPs and Au-DOX conjugation (100 μM of DOX or 4 μL of Au)
Ag and TiO2 based NPs	Non-applicable	In vitro: murine B16F10 cell line	Cell viability assay: MTT (75, 100, 150 and 200 μg/mL)	The formulation allied to PTT treatment markedly reduced tumor cells viability in vitro as well as the tumor volume in an in vivo model.	[173]
		In vivo: male and female C57BL/6J mice; s.c. injection of B16F10 cells	i.t. administration of formulation (100 μg/mL) followed or not by PTT application (808 nm; 2 W/cm2, 1 min)
Fe3O4 and Au based NPs	Non-applicable	In vivo: male C57BL/6 mice; s.c. injection of B16F10 cells	i.v. administration of NPs (150 μg Au/mL) with and without PTT treatment (808 nm; 2.5 W/cm2, 6 min)	The magnetically target NPs associated with PTT impaired significantly the tumor growth in comparison to control group.	[174]

Abbreviations: Ag, silver; AgPt NPs, silver and platinum nanoparticles; AO, acridine orange; Au, gold; Au NPs, gold nanoparticles; BCA, bicinchoninic acid; Cu NPs, copper nanoparticles; Cu₂O NPs, cuprous oxide nanoparticles; DAPI, diaminidino phenylindole; DOX, doxorubicin; EtBr, ethidium bromide; Fe₃O₄, iron(II, III)oxide; FITC, fluorescein isothiocyanate; H₂DCFDA, dichlorodihydrofluorescein diacetate; i.t., intratumoral; i.v., intravenous; JC-1, tetrachloro tetraethylbenzimidazolylcarbocyanine iodide; MoO₃ NPs, molybdenum trioxide nanoparticles; MTS, dimethylthiazol carboxymethoxyphenyl sulfophenyl tetrazolium; MTT, dimethylthiazol diphenyl tetrazolium bromide; NPs, nanoparticles; NRU, neutral red uptake; Pd NPs, palladium nanoparticles; PI, propidium iodide; POR, porphyrin derivate—Tetrakis-5,10,15,20-(2,4-dihydroxyphenyl)porphyrin; ROS, reactive oxygen species; s.c., subcutaneous; SRB, sulphorodamine B; TiO₂, titanium dioxide; TMA-DPH, trimethylamonium diphenyl hexatriene.