Intracellular Delivery of Nanocarriers for Cancer Therapy

Drug delivery systems largely contribute to cancer therapy in terms of tumor targeting and controlled release of cargo molecules. While targeting of tumor “tissue” has been achieved using nanocarriers, delivery of cargo molecules into tumor cells is still challenging. Intracellular delivery of nanocarriers is an essential process to overcome multi-drug resistance and for the delivery of cargo molecules for both therapy and vaccine applications. Nanocarriers may gain access to the interior of target cells either non-specifically, as in adsorptive endocytosis, or specifically, as in receptor-mediated endocytosis. Once internalized, they must subsequently break free of their endosomal compartments in order to deliver their cargo into either the cytosol or nucleus. If the nucleus is the target, as in DNA delivery, the nanocarrier must then traffick to the perinuclear region and deliver the cargo into the nucleus, either by physically transporting DNA through the nuclear pore complex (NPC), or by releasing DNA at the door of the NPC, allowing free DNA to gain access. This review article includes both principles and mechanisms of intracellular delivery of nanocarriers, and gives a few examples of their application.