Application of chloroquine as an endosomal escape enhancing agent: new frontiers for an old drug

Adequate transfection efficiency is indispensable to safe and effective delivery of therapeutically active agents, particularly in cancer. Endosomal escape is regarded as a critical and determining step devoted a significant number of studies of the drug/gene delivery field.

This paper critically reviews the fundamental properties of chloroquine (CQ), its pharmacokinetics, pharmacodynamics, and clinical applications and the present knowledge of CQ application as an endosomal escape enhancing agent. Different approaches to enhance the endosomal escape process of nanoparticles have been introduced including use of endosomal escape enhancing agents. Application of CQ as either a pre-treatment modality in which cells or animals are exposed to CQ prior to the main treatment or a component of co-delivery systems where CQ and other anti-cancer agents are simultaneously entered the cancer cells, is discussed with recent studies.

CQ is founded to intervene with the natural process of endosomal maturation. Moreover, CQ seems to increase the effectiveness of gene delivery by its electrostatic interaction with negatively charged components of the transferred genetic molecules. Endosomal escape might be regarded as the bottleneck of efficient gene delivery and CQ as an effective and available endosomal escape enhancing agent deserves more sophisticated studies.