Table 4.

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

Nanosystem Composition	Compound(s)	Model(s)	Summary of Experimental Assays and Conditions	Main Conclusions	Reference
Chitosan	S-nitroso-MSA	In vitro: murine B16F10 cell line	Cell viability assays (5, 10, 20, and 40 μg/mL): MTT, trypan blue and LDH release ROS detection assay: CM-H2DCFDA and MitoSOX Red Cell death assays: annexin V-FITC/PI and caspase-3 activity	Nanoformulation exhibited high cytotoxicity selectively on cancer cells.	[145]
PLGA and PVA	Xanthohumol	In vitro: murine B16F10 cell line	Cell viability assay: MTT (2 to 40 μM) Cell proliferation assay: wound healing	Loaded PLGA NPs showed high cytotoxicity as well as inhibition of proliferation and migration.	[146]
PMMA and sodium lauryl sulfate	α-terpineol	In vitro: murine B16F10 and human SK-MEL-28 cell lines	Cell viability assay: MTT (5, 50 and 500 μg/mL)	Nanosystem exhibited a large and selective cytotoxic effect in both melanoma cell lines tested.	[149]
PLA and PVA	DTIC and zinc phthalocyanine	In vitro: human MV3 cell line	Cell viability assay: MTT (20 and 100 μg of DTIC) after PDT application (660 nm; 28 J/cm2, 2.5 min)	In vitro assays demonstrated the added value of combined therapy in reducing cancer cell viability.	[150]
PLGA and PVA	ICG and NextA	In vitro: murine SM1 and B16F10 cell lines	Cell viability assay: Cell Titer-Glo ATP (0.5 to 2.0 mg/mL of NPs) with and without application of PTT HDAC activity assay: HDAC-Glo I/II	The combination of photothermal and epigenetic therapies increased the in vitro expression of immunological markers. Moreover, in an in vivo context, a delayed tumor progression and an improved median survival were achieved.	[151]
		In vivo: female C57BL/6 mice; s.c. injection of SM1 cells	i.t. administration of different formulation combinations (50 mg/kg of NPs) followed or not by PTT application (808 nm; 0.4 W, 10 min)
PLGA and poloxamer 407	Apatinib	In vitro: murine B16 cell line	Cell viability assay: CCK-8 solution (4, 20 and 40 μg/mL)	In vitro and in vivo experiments demonstrated the high performance of Apa-PLGA NPs.	[152]
		In vivo: male C57BL/6 mice; injection of B16 cells	i.t. administration of free apatinib at different concentrations (2, 4 and 6 mg/kg), empty PLGA NPs and Apa-PLGA NPs (6 mg/kg)
PCL, span 80, caprylic/caprictriglycerides and polysorbate 80	Resveratrol	In vitro: murine B16F10 cell line	Cell viability assay: MTT (1, 3, 10, 30, 100 and 300 μM)	Confirming the in vitro cytotoxicity results, the in vivo study demonstrated an increase in areas of inflammation and necrosis as well as a reduction of metastases and pulmonary hemorrhage compared to the free compound.	[153]
		In vivo: male and female C57BL/6J mice; s.c. injection of B16F10 cells	i.p. administration of free resveratrol, empty PCL NPs and resveratrol-PCL NPs (5 mg/kg)
Chitosan, sodium alginate and calcium chloride	DOX	In vitro: murine B16F10 and B16OVA cell lines	Cell viability assay: alamar blue solution (1 to 100 μM)	In vitro assays suggested a greater intracellular accumulation and cytotoxicity of the nanosystem compared to the free drug. However, a similar effect between both was observed in the in vivo inhibition of tumor progression.	[154]
		In vivo: female C57BL/6 mice; s.c. injection of B16OVA cells	i.v. injection of free DOX, empty NPs and DOX NPs (3 mg/kg)

Abbreviations: Apa, apatinib; CCK-8, cell counting kit-8; CM-H₂DCFDA, chloromethyl dichlorodihydrofluorescein diacetate; DOX, doxorubicin; DTIC, dacarbazine; ICG, indocyanine green; FITC, fluorescein isothiocyanate; HDAC, pan-histone deacetylase; i.p., intraperitoneal; i.t., intratumoral; i.v., intravenous; LDH, lactate dehydrogenase; MTT, dimethylthiazol diphenyl tetrazolium bromide; NextA, nexturastat A; NPs, nanoparticles; PCL, poly(ε-caprolactone); PDT, photodynamic therapy; PI, propidium iodide; PLA, polylactic acid; PLGA, poly lactic-co-glycolic acid; PMMA, poly(methyl methacrylate); PTT, photothermal therapy; PVA, polyvinyl alcohol; s.c., subcutaneous; S-nitroso-MSA, S-nitrosomercaptosuccinic acid.