Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review

Table 1

Particular nanocarrier structural components for improving drug targeting to the tumor tissue.

Components for successful targeted drug delivery in antitumor	Benefits in anticancer therapy	References
Active targeting
Cholesterol	Cancer cells take up 100-fold more low density lipoprotein (LDL) than normal tissue due to upregulated LDL receptors in cancer cells for membrane synthesis during cell division associated with malignant transformation processes. Thus, LDL has been proposed as a drug carrier for anticancer agents.	[208, 239–245]
Polyunsaturated fatty acids (α-linolenic acid; linoleic acid; arachidonic acid; eicosapentaenoic acid; and docosahexaenoic acid).	They can be attached to the tumor cell membrane more easily, which results in disruption and fluidity of the cell membranes. Tumor progression is reduced by modulating p53, p16, and p27 expression and cell cycle regulation, as well as by inducing cell death by apoptosis and necrosis.	[246–248]
Hyaluronic acid	Hyaluronic acid is an extracellular matrix compound that specifically binds CD44, which is an extracellular membrane protein that regulates various cellular responses. CD44 is overexpressed in cancer cells, while normal cells underexpress this protein. Thus, CD44 is a good candidate biomarker for cancer cells.	[249–251]
Folic acid	Folate is important for producing and maintaining new cells because it can participate in nucleotide synthesis. Folates receptors are highly overexpressed in cancer cells. In addition, only the malignant cells, not normal cells, transport folate-conjugates; thus, the folate-drug conjugation can improve tumor-targeted drug delivery.	[248, 252–254]
Passive targeting
Polysaccharides; polyacrylamide; polyvinyl alcohol; polyvinylpyrrolidone; PEG; PEG-containing copolymers (poloxamers; poloxamines; polysorbates; and PEG copolymer).	They prevent the opsonin binding to the nanoparticle surfaces and, consequently, recognition as well as phagocytosis of the nanoparticles by the mononuclear phagocytic system, which enhances the blood circulation time.	[212, 255–258]
Cationic surfactants	The positive charge of a cationic surfactant interacts through electrostatics with the negatively charged phospholipids that are preferentially expressed on the cancer cell surface.	[252, 259–261]