Innovative Technologies in Nanomedicines: From Passive Targeting to Active Targeting/From Controlled Pharmacokinetics to Controlled Intracellular Pharmacokinetics

Nanomedicines promise to extend drug therapy from small molecular compounds to proteins/nucleic acids/genes. Multifunctional envelope‐type nanodevices (MENDs) have been developed for delivering such molecules to the site of action. The YSK‐MEND contains new types of pH‐responsive cationic lipids to efficiently deliver siRNA to hepatocytes via receptor‐mediated endocytosis and use in treating hepatitis C and B in model mice. The RGD ligand is introduced to target tumor endothelial cells (TEC) and RGD‐MEND is able to send siRNA to TEC to regulate the function of tumor microenvironments. The MITO‐Porter is also developed to target mitochondria via membrane fusion. Antisense oligo RNA in the MITO‐Porter permits the knock down of mitochondrial function. Finally, the ssPalms is designed based on a new concept of pH‐dependent protonation in endosomes and cleavage of SS bonds in the reducing conditions in cytosol. These new technologies promise to stimulate the use of Nanomedicines in the future. Multifunctional envelope‐type nanodevice (MEND) is developed for Nanomedicines. The YSK‐MEND composed of pH‐responsive cationic lipids can successfully deliver siRNA to hepatocytes efficiently in vivo and it is extended to target tumor endothelial cells with RGD ligand for active targeting. A derivative form of YSK‐MEND can also applicable for siRNA delivery to immune cells.