Loading-free supramolecular organic framework drug delivery systems (sof-DDSs) for doxorubicin: normal plasm and multidrug resistant cancer cell-adaptive delivery and release

Abstract

Four water-soluble porous supramolecular organic framework drug delivery systems (sof-DDSs) have been used to adsorb doxorubicin (DOX) in water at physiological pH of 7.4, which is driven exclusively by hydrophobicity. The resulting complexes DOX@SOFs are formed instantaneously upon dissolving the components in water. The drug-adsorbed sof-DDSs can undergo plasm circulation with important maintenance of the drug and overcome the multidrug resistance of human breast MCF-7/Adr cancer cells. DOX is released readily in the cancer cells due to the protonation of its amino group in the acidic medium of cancer cells. In vitro and in vivo experiments reveal that the delivery of SOF-a-d remarkably improve the cytotoxicity of DOX for the MCF-7/Adr cells and tumors, leading to 13-19-fold reduction of the IC50 values as compared with that of DOX. This new sof-DDSs strategy omits the indispensable loading process required by most of reported nano-scaled carriers for neutral hydrophobic chemotherapeutic agents, and thus should be highly valuable for future development of low-cost delivery systems.