In situ-prepared homogeneous supramolecular organic framework drug delivery systems (sof-DDSs): Overcoming cancer multidrug resistance and controlled release

Water-soluble three-dimensional porous supramolecular organic frameworks (SOFs) have been demonstrated as a new generation of homogeneous polycationic platforms for anti-cancer drug delivery. The new SOF drug delivery systems (sof-DDSs) can adsorb dianionic pemetrexed (PMX), a clinically used chemotherapeutic agent instantaneously upon dissolving in water, which is driven by both electrostatic attraction and hydrophobicity. The in situ-prepared PMX@SOFs are highly stable and can avoid important release of the drug during plasm circulation and overcome the multidrug resistance of human breast MCF-7/Adr cancer cells to enter the cancer cells. Acidic microenvironment of cancer cells promotes the release of the drug in cancer cells. Both in vitro and in vivo studies have revealed that sof-DDSs considerably improve the treatment efficacy of PMX, leading to 6-12-fold reduction of the IC50 values, as compared with that of PMX alone. The new drug delivery strategy omits the loading process required by most of reported nanoparticle-based delivery systems and thus holds promise for future development of low-cost drug delivery systems