Where is the drug gone? - Measuring intracellular delivery and localization

摘要

An ability to direct and control intracellular uptake of drugs, genes and nanoscale materials is a prerequisite for applications in different biomedical contexts [1]. Targeted drug delivery provides imminent therapeutic control of many diseases including the biggest killers such as cardiovascular and genetic disorders as well as metastatic cancers. Recent initiatives in industry, venture capital and national research programs build upon the need for more efficient and quantitative intracellular delivery [2], which also emphasise the criticality of harmonised legislation and suitable standards for advanced therapy medicinal products (200 1831 EC - 20081291 EC). From the outset of drug delivery, main efforts have been focused on those approaches that can ensure appreciable therapeutic uptake into the cell, but barriers to overcome remain in the poor permeability of cellular membranes, which are often accompanied by low aqueous solubility of drugs [3]. To address these shortcomings small-molecule drugs are structurally optimised to afford better lipophilicity-to-solubility ratios, while bio-macromolecules, notably protein transduction domains, find increasing use as facilitators of active drug-membrane traversal. Conjugation- and complexation-based strategies are used to generate delivery systems with auxiliary functionalities promoting endosomal escape and nucleus targeting [4], which makes macro-molecular transport an enabling strategy for gene therapies [5].