Deploying drugs throughout the body via a patient's bloodstream is not only wasteful, but can also have adverse effects on healthy tissues. Minimizing such side effects not only allows higher doses to be administered at the site of need, but also increases patient compliance. Targeted or 'smart' drug-delivery is a means of consigning a therapeutic payload to specific locations within the body, and metal–organic frameworks (MOFs) appear ideal candidates for such a purpose: they can be made relatively easily, they have large pores capable of hosting drug molecules and have well-defined molecular structures. What's more, frameworks with extra functionalities can be created by carrying out further chemistry after their initial fabrication in a process termed post-synthetic modification (PSM).
Now, in a collaboration between Jilin University and Beijing Institute of Technology, Ying-Wei Yang, Bo Wang and co-workers have fabricated just such a material. Following self-assembly of zinc ions and dicarboxylate ligands into nanosized MOFs, the team covalently decorated the outer surfaces with pyridinium pendants through PSM. Their pores were charged with an active payload — either rhodamine 6G (a fluorescent dye) or doxorubicin hydrochloride (an anti-cancer drug) — and then capped by anionic 'pillarenes', which are bulky macrocycles. The binding of these anions was through encapsulation around the cationic pyridinium pendants. This capping was sufficiently effective that the pore openings were blocked and release of the payload in this state was negligible.
Exposure of the MOFs to an acidic environment, such as is present in the vicinity of tumour cells, causes protonation of the pillarenes and their dissociation from the framework surface. With the pores uncapped, the active payload is released into the surrounding medium. Additionally, the MOF possesses properties that are key for in vivo implementation, namely, low cytotoxicity with good biodegradability and good biocompatibility. The nanosized crystals are also small enough to be taken up by cells.