Since most cells are not able to take up naked nanoparticles (except for reticuloendothelial cells and macrophages) the addition of targeting ligands is necessary to reach certain cells or organelles. Those ligands bind to cell/organelle unique receptors that can be either protein, carbohydrate or lipid based.
After that, they can be internalized through several paths to deliver the drug in the cells, which will highly depend on the stability of the compound and the aim of the delivery. For example, in some cases biological materials introduced into cells via endocytosis lose their biological activity due to contact with acidic media. In these cases, the use of fusogenic liposomes are an alternative to the release of drugs like in gene therapy. The high efficiency of this system is attributable to the fact that materials introduced by membrane fusion can escape lysosomal degradation and reach the cytoplasm in an intact form.
- Release at the therapeutic target
- Controlled biodistribution
- Enhancement of permeability and retention effects
- Reduction of toxic side effects
- Reduced dose
- High circulation times
- Increased treatment efficacy
- Intracellular delivery: Delivery of the encapsulated compound inside the cell can be done through various routes. Some examples are transfer of lipophilic compounds, intracellular fusion, liposome internalization, TAT-peptide translocation, and membrane fusion.
- Cancer treatment: Tumor masses present what is referred to as enhanced permeability and retention effect (EPR). They develop its own vasculature that enable particles up to 200 nm to leak to the cancer site. However, in many cases, the addition of a ligand is also used to enhance the delivery in those cancer cell types. Some examples are monoclonal antibodies, peptides, folate, or transferrin.
- Brain targeting: Different targeting ligands such as antibodies and aptamers can be used to enhance drug accumulation in the brain. Another example of ligands used could be glutathione, methoxy-XO4, insulin, thiamine, peptides, and transferrin.
- Ocular delivery: Studies have shown that addition of RGD peptide ligand onto the surface of the nanocarrier targets corneal epithelial cells. This enables both the endocytosis of the nanovehicle as well as the specific release of the drug in the ocular tissue.
- Diabetes: Although Type 1 diabetes has always been considered an irreversible autoimmune disease, some cell types, like Treg, are able to restore immune tolerance and suppression of the disease development. Liposomes targeted towards Treg cells have successfully been used to release therapeutic levels of immunomodulators, improving the autoimmune response.