Improved understanding of the molecular mechanisms of diseases results in the rational development of drugs, which are designed to act at specific sites within cells. Irrespective of its size, such a drug must safely reach not only its target cell but also the appropriate location within the target cell to achieve the desired therapeutic effect. In the simplest scenario, small molecule drugs enter cells by diffusion and reaching the desired subcellular location is comparatively unproblematic. Unlike small molecule drugs, macromolecular drugs such as proteins, nucleic acids, and synthetic polymer-drug conjugates are restricted to fewer subcellular compartments due to their large size. Macromolecules cannot cross cell membranes by simple diffusion and are usually internalized by endocytosis. The limited ability of macromolecules to enter cells is widely exploited to their advantage by attaching ligands to macromolecules that can target them to specific cells; capitalizing on the unique expression of some plasma membrane receptors and antigens in certain cells or diseases. However, even after the internalization by endocytosis, the macromolecules remain separated from the intracellular space by a biological membrane. Efficient delivery of therapeutic macromolecules to designated subcellular locations therefore greatly relies upon successful passage across biological membranes. For example, delivery of macromolecules to the most important subcellular target, which is the nucleus, requires crossing two biological membranes. Improved understanding of differences in membrane function, properties, and structure among cellular organelles contributes to better control of subcellular delivery and targeting of drugs and becomes increasingly important for the development of macromolecular therapeutics.
|Original language||English (US)|
|Title of host publication||Biomaterials for Delivery and Targeting of Proteins and Nucleic Acids|
|Number of pages||28|
|State||Published - Jan 1 2004|
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)