Nanoparticles for targeted drug delivery in chemotherapy

Abstract

Nanoparticle-based targeted drug delivery has been an interesting topic for researchers during several past decades. Sophisticated delivery systems are especially important in cancer chemotherapy to localize the drug at specific site of the body and reduce toxic effects. However, many nanoparticles for cancer treatment are passively targeting systems and based on the enhanced permeation and retention (EPR) effect. In this case majority of nanoparticles may accumulate in such organs, as liver, spleen, and lungs. Alternatively, actively targeting nanoparticles are conjugated with a ligand/carrier interacting with the specific target in cancer cells, and this strategy could improve drug localization in tumor. Most solid tumors are characterized by hypoxia, and it is a prognostic indicator of a poor clinical outcome for patients. Many hypoxia-targeted cancer therapies are based on carbonic anhydrase IX (CA IX), a membrane protein which is highly overexpressed in numerous cancers, but is largely absent in normal tissues. Several inhibitors selective to CA IX have been synthesized. A sulphonamidic compound VD11-4-2 possesses a high affinity (about 50 pM) and excellent selectivity towards CA IX. We applied VD11-4-2 as a specific cancer targeting agent in both passive and active targeting nanosystems. [...].