Table 2.

Cell line studies using nano-agents for treatment of melanoma

Formulation	Cell lines used	Results	References
Liposomes containing pH-responsive phytosterol derivatives	B16-F10	Contents delivered into endosomes and cytosol of B16-F10 cells Liposomes penetrated 3D skin models and reached basement membrane	Yamazaki et al. (2017)
Liposomes containing ferrous chlorophyllin	B16-F10	Increased cellular uptake of liposomes via endocytosis Preferential accumulation in mitochondria and nucleus Decreased LC50 with increased incubation time after PDT Mechanism of cell death: apoptosis and necrosis	Gomaa et al. (2017)
Curcumin-loaded liposome gold nanoparticles	B16-F10	Significant temperature rise upon laser irradiation causing irreversible cellular damage Significantly enhanced cellular uptake Enhanced cancer cell cytotoxicity upon laser irradiation	Singh et al. (2017)
Liposomes containing C6 (ceramide)	SK-Mel2, WM-266.4, A-375, WM-115	Caspase-dependent apoptotic death Activated protein phosphatase 1 (PP1) to inactivate Akt-mammalian target of rapamycin (mTOR) signaling, inhibiting melanoma cells	Jiang et al. (2016)
Liposomes containing Cuphen	MNT-1 HaCaT B16-F10	Anti-proliferative effects of Cuphen in different cancer cell lines, in free form or after incorporation in liposomes Main function of liposomes was to enhance stability of Cuphen and its accumulation in cancerous tissues via EPR effect	Nave et al. (2016)
pH-sensitive liposomes containing doxorubicin	A375	Fused with endosomal membrane under acidic conditions of endosome to release doxorubicin into cytoplasm, gathered into nucleus, thus achieving “endosomal escape” Lower cell viability under low pH conditions	Xu et al. (2015)
Layer-by-layer polymer-coated gold nanoparticles containing imatinib mesylate	B16-F10	Iontophoresis application enhanced skin penetration of nanoparticles by 6.2-fold as compared to passive application Greater retention in stratum corneum and viable skin Rapid uptake Significant decrease in cell viability	Labala et al. (2015)
Gold Nanoparticles	HTB-72	After irradiation, progression of treated cells towards G2/M phase was more rapid than that of non-treated cells, release of former from G2/M phase was slower than that of latter Irradiation with gold nanoparticles increased vulnerability of cells to radiation damage	Kim and Kim, (2018)
Gold nanoparticles and mitoxantrone with microwave hyperthermia	DFW	Mitoxantrone and gold nanoparticles under irradiation caused maximum cell death compared to other groups	Shanei et al. (2017)
Gold nanoparticles combined with antibodies targeting phosphorylated FAK (p-FAK-GNP)	G361 HaCaT	Used non-thermal atmospheric pressure plasma to stimulate gold nanoparticles within p-FAK-GNP Much higher lethality of combined treatment against G361 cells than HaCaT keratinocyte cells Immediate killing of G361 cells by plasma and p-FAK-GNP	Choi et al. (2017)
Phthalocyanines attached on surface of gold nanorods	B16-F10 B16-G4F	Photodynamic properties of phthalocyanines were enhanced Combination of PDT and hyperthermia eliminated over 90% of melanoma cells	Freitas et al. (2017)
PEGylated gold nanoparticles	B16F10	Proliferation efficiency and survival fraction decreased with increasing concentration of nanoparticles Significant sensitization of nanoparticles and radiosensitization occurred in presence of 6 MeV electrons	Mousavi et al. (2017)
Chitosan-coated gold nanoparticles carrying STAT3 siRNA	B16-F10	Inhibited cell growth by 49.0 ± 0.6 and 66.0 ± 0.2% at 0.25 nM and 0.5 nM STAT3 siRNA concentration, respectively Time dependent cell uptake up to 120 min Clathrin mediated endocytosis as predominant cell uptake mechanism Apoptosis assay showed 29 and 44% of early and late apoptotic events Application of anodal iontophoresis enhanced skin penetration to reach viable epidermis	Labala et al. (2016)
Curcumin-loaded gold nanoparticles	B16-F10s	Efficient uptake and decreased cell viability compared to free curcumin	Muddineti et al. (2016)
Chitosan-coated gold nanoparticles as hidden cargo of endothelial colony forming cells (ECFCs)	A375	Heavily Gold-doped ECFCs efficiently warmed up tumor environment and killed cancer cells via hyperthermic heating both in vitro and in vivo	Margheri et al. (2016)
Lipid-coated gold nanohybrids containing docetaxel	B16-F10	Significantly greater cytotoxicity compared to free docetaxel Improved cellular uptake Effective tumor cell suppression	Kang and Ko (2015)
Anti-NEU antibody-labeled gold nanoparticles	G361 HaCaT	Preferentially targeted melanoma cells than normal keratinocytes Melanoma cells had higher death rate than normal keratinocyte cells Cancer cell death was due to selective destruction of NEU protein and downstream effector of NEU	Choi et al. (2015)
Gold nanoparticles surrounded by amphiphilic-mixed organic ligand shell	B16-F10	Amphiphilic nanoparticles initially delivered into endosomes by gold core transferred over a period of hours to intracellular membranes through tumor cells Greater intracellular spread in melanoma cells than breast carcinoma cells Enhanced radiotherapeutic killing of melanoma cells	Yang et al. (2014)
Carbon nanotube, multi-walled carbon nanotube, iron oxide nanoparticles	F10	All nanoparticles induced selective toxicity and caspase 3 activation through mitochondria pathway Caused generation of ROS, mitochondrial membrane potential decline, mitochondria swelling and cytochrome c release	Naserzadeh et al. (2017)
Zinc monoamino phthalocyanine–folic acid-conjugated single-walled carbon nanotubes	A375	60–63% cell death after irradiation of treated melanoma A375 cells	Ogbodu et al. (2015)
Anti-GD2 antibody-attached gold nanoparticle conjugated, single-wall carbon nanotube (SWCNT)	UACC903	Huge enhancement of two-photon luminescence intensity due to strong resonance enhancement coupled with stronger electric field enhancement Serves as local nanoantennae to enhance photothermal capability via strong optical energy absorption Selective two-photon imaging using 1100 nm light 100% melanoma cells killed after 8 min of exposure	Tchounwou et al. (2015)
Coffee oil–algae oil-based nanoemulsions	B16 F10	Effective inhibition of melanoma cell growth Cell cycle arrested at G2/M phase Dose-dependent upregulation of p53, p21, cyclin B, and cyclin A, bax, and cytochrome c expressions and downregulation of CDK1, CDK2 and bcl-2 expression Rise in caspase-3, caspase-8, and caspase-9 activities for apoptosis execution	Yang et al. (2017)
Oil-in-water nanoemulsions of tectona grandis leaf extract	B16 F10	Possessed ability to sensitize cells to red light of LED in vitro Photodynamic effect observed as toxicity increased under illumination with red light Reasonable photocytotoxicity and much less toxic towards normal cells in dark	de Menezes Furtado et al. (2017)
Nanoemulsion of 5-FU	SK-MEL-5	Much more efficacious than free 5-FU when used for topical delivery	Shakeel et al. (2015)
Multi-peptide and toll-like receptor 4 agonist codelivery system based on lipid coated Zinc phosphate hybrid nanoparticles	B16-F10	Exhibited anti-tumor immunity evident by secretion of cytokines in vitro and increased CD8+ T-cell response from IFN-γ ELISPOT analysis ex vivo Improved anti-tumor effects evidenced from prophylactic, therapeutic and metastatic melanoma tumor models compared with free antigens and single peptide-loaded nano-vaccines	Zhuang et al. (2016)