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 sofDDSs 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

Molecular bases of Sorcin-dependent resistance to chemotherapeutic agents

Soluble resistance-related calcium binding protein(Sorcin)is a protein initially labelled“resistance-related”,since it is co-amplified with ABCB1 in multidrug(MD)-resistant cells.While for years Sorcin overproduction was believed to be a by-product of the co-amplification of its gene with the P-glycoprotein gene,many recent studies view Sorcin as an oncoprotein,playing an important role in MD resistance(MDR).Sorcin is one of the most highly expressed calciumbinding proteins,which is overexpressed in many human tumors and MD resistant cancers,and represents a novel MDR marker.Sorcin expression in tumors inversely correlates with patients’response to chemotherapies and overall prognosis.Sorcin is highly expressed in MDR cell lines over their parent cells.Sorcin overexpression by gene transfection increases drug resistance to a variety of chemotherapeutic drugs in many cancer lines.On the other hand,Sorcin silencing leads to reversal of drug resistance in many cell lines.This review describes:(1)the roles of Sorcin in the cell;(2)the studies showing Sorcin overexpression in tumors and cancer cells;(3)the studies showing the effects of Sorcin overexpression and silencing;(4)the molecular effects of Sorcin overexpression;and(5)the structural and genetic bases of Sorcin-dependent MDR.