چگونگی تنظیم نانوذرات و تاثیر آن در بهبود رسانش دارو How can we fine-tune nanoparticles to improve drug delivery?

Approaches to enhanced therapeutic efficiency of nanoparticles Conjugation of targeting ligands The specificity of drug-delivery efficacies in nanoparticles can be achieved by successfully conjugating cell-specific ligands onto the nanoparticle surface. For example, in oncology, nanoparticles can be designed to integrate targeting ligands which bind to receptors that are only expressed in tumorous cells and not healthy cells. Cancer-associated biomarker molecules include the following: families of vitamin receptors such as the FA vitamin B9 receptors (FAR-α, FAR-β), riboflavin (vitamin B2) receptor and biotin receptor; the αvβ3 integrin receptor; PSMA receptor; growth factor receptors like Her2, EGFR and FGFR; insulin and insulin-like receptors; a family of selectin protein molecules; and transferrin receptor. In the conjugation of the targeting ligands to nanoparticles, multiple ligand molecules will be attached to the nanoparticle surface [7]. This is because, in order for endocytic uptake of such targeted nanoparticles to occur, there needs to be multiple interactions existing concurrently between the interface of the cell surface receptor and targeted ligand pairs. This multivalent binding mechanism confers tight adhesion of the nanoparticle onto the targeted cell surface. This aspect is considered to be highly important during receptor-mediated uptake (endocytosis) of nanoparticles by the cell. Without it, the nanoparticles are bound weakly and have too short of a residence time to get taken up through the formation of coated pits. Therefore, by covalently conjugating many copies of a targeting ligand onto the nanoparticle surface, it maximizes these multivalent effects [8]. The challenge that we are facing is that the constitutive expression may still occur in healthy cells and therefore, tumorous and healthy cells may share the same ligand expression. A result of this is that, healthy cells can also absorb nanoparticles conjugated with targeted ligands when this happens, therapeutic efficiency of the administered drug is reduced. If the drug is toxic, cytotoxicity is another consequence.