Multi-responsive Glyco-target Cationic Vesicles Based On Pillar[5]Arene And Galactose Derivative

Cancer chemotherapy has two major problems: one is side effects on normal cells, and the other one is multidrug resistant of cancer cells. Research shows that we can use the differences of surface receptors between cancer cells and normal cell, be modified specifically recognizes receptor target moiety in the pharmaceutical carrier, thereby it can enter target cancer cells selectively; furthermore we can controll the drug release by modified responsible group on the drug carrier using the microenvironment differences of cancer cells and normal cells, to achieve the reduction of drug toxicity to normal cells. Further, cancer cells can be silenced by loading the drug carrier siRNA associated with a drug resistance gene to inhibit cancer cell resistance continually occurring. In recent years, scientists have devised a number of biocompatibility, low toxicity, controllability vesicle drug delivery systems. Pillararene as a new generation of macrocyclic molecules, because of its easy modification, unique electronic cavities, etc., has a very broad application prospects in terms of drug-loaded nanoparticles. Therefore, the present study was to use molecular aromatic hydrocarbon pillararene as the host macrocyclic molecule, galactose pyridine salt derivative as a guest molecule, with the host-guest supramolecular self-assembled amphiphilic molecules in aqueous solution to build a new type of cationic vesicles by hydrophilic and hydrophobic effects. The redox- and pHresponsive vesicle is expected to achieve drugs/siRNA codelivery.(1) Preparation of redox- and pH- responsive glyco-target amphiphilic supramolecular systems:We use the new macrocyclic aromatic molecules pillararene and cysteamine derivatives to obtain a novel host molecule by clicking. Furthermore, galactose as a good target group, galactose can be modified as galactose pyridine salt derivatives, it can be used as a gust molecular, to obtain the desired redox- and pH- responsive glyco-target amphiphilic supramolecular systems.(2) Redox- and pH- responsive glyco-target cationic vesicles constructed:Pillararene derivatives and galactose pyridinium derivative form amphiphilic molecules by self-assembled in aqueous solution target cationic redox-pH double sugar response by hydrophilic and hydrophobic effects. We characterize the vesicles by scanning electron microscope, surface tension meter and dynamic light scattering Zetasizer Nano, etc. The prepared vesicles were characterized by in vitro experiments and release the drug, verify nanovesicles drug has a higher load factor, both Redox-pH double response. The derivates in a neutral aqueous solution, the amino group may form water-soluble cationic amino root, siRNA load is expected to negatively charge. Based on this, the vesicles is expected to simultaneously solve two major problems in cancer chemotherapyIn summary, redox- and pH- responsive vesicle is expected to achieve drugs/siRNA codelivery, so as to solve two major problems in cancer chemotherapy.