Acid-labile Molecular Container for Controlled Drug Release Developed

In a recent study, Research Associate Professor Liu Jia from SIAIS and Professor Ma Da from Fudan University developed an acid-labile acyclic cucurbit[n]uril (CB[n]) molecular containers for controlled drug release. Their study was published in Angewandte Chemie International Edition.

Pathological conditions such as tumors often lead to acidic microenvironment, making acid-labile drug carriers attractive topics for drug development. These acid-labile drug carriers can mediate highly efficient drug release under acidic microenvironment, thus enhancing the specificity of drug molecules. Acid-labile liposome, inorganic and organic nanoparticles and polymer-drug conjugates have been reported in previous studies. In this study, the teams led by Professor Ma and Professor Liu re-designed biocompatible acyclic CB[n] molecular containers, enabling them to respond to acidic pH.

Chemical modification of cationic CB[n] containers with citraconic anhydride, maleic anhydride or succinic anhydride masks the amino groups on the arms of CB[n] containers with amide, converting the positively charged containers to negatively charged containers while maintaining their affinity to cargo molecules. The team found that these modifications render corresponding containers different levels of stability under an acidic environment. By a proof-of-principle study with proflavine, the team showed that acid-labile molecular container can promote cellular uptake of cargo molecules under acidic microenvironment.

Graduate student Mao Dake from Fudan University’s Department of Chemistry and postdoctoral fellow Liang Yajun from SIAIS at ShanghaiTech University are co-first authors of this study, and Professors Ma and Liu are co-corresponding authors. This study was supported by Natural Science Foundation of China and ShanghaiTech University.

Details of this study can be found at: http://onlinelibrary.wiley.com/doi/10.1002/anie.201707164/abstract

                    Note: Mechanism of action of acid-labile molecular containers