Abstract:
Pharmaceutical nanocarriers, including liposomes and polymeric micelles, are frequently used for the delivery of a broad variety of both soluble and poorly soluble anticancer drugs to enhance their in vivo efficiency. The next generation of drug delivery systems for cancer, especially, for multidrug resistant (MDR) tumors, includes multifunctional stimuli-responsive nanocarriers, i.e. nanocarriers that can circulate long; target the site of the disease; respond local stimuli characteristic of the pathological site by, for example, releasing an entrapped drug or deleting a protective coating to facilitate the contact between drug-loaded nanocarriers and target cells; and even provide an enhanced intracellular delivery of the drug with its subsequent delivery to specific intracellular organelles. Among new developments to be considered in the area of multifunctional pharmaceutical nanocarriers for MDR tumors are: drug- or/and siRNA-loaded delivery systems additionally decorated with cell-penetrating peptides for the enhanced intracellular delivery; “smart” multifunctional drug delivery systems, which can reveal/expose temporarily hidden functions under the action of certain local stimuli characteristic for the tumor microenvironment (such as lowered pH, redox-conditions, hypoxia, or locally increased expression of certain enzymes); new means for controlled delivery and release of siRNA; and approaches for intracellular drug delivery and organelle targeting. The application of nanocarriers co-loaded with siRNA and drugs to treat specifically MDR tumors will be specifically addressed.
