Antitumor Activity Of Bipyridinium Ion And It's Mediated Fenton System

Among current cancer treatment strategies,chemotherapy is still an important method to overcome cancer.Although some impressive progress has been made to improve the status of poor control of cancer metastasis,severe drug resistance and extremely strong drug-induced side effects,the efficacy of existing drugs is quite limited.Therefore,there is an urgent need to discover and develop new effective therapeutic agents with high targeting,low toxicity and no drug resistance.This article summarized and analyzed the role of amphiphilic cationic drugs in anti-tumor,the interaction between intracellular ROS(reactive oxygen species)and tumors,and the application of pyridinium ions in drug delivery systems.A series of 4,4'-bipyridinium salt compounds were synthesized by the reaction of 4,4'-bipyridine alkylation.The structure of the target product has been verified by means of nuclear magnetic hydrogen spectrum,carbon spectrum and other means,and the target product has been tested for in vitro cytotoxicity.Preliminary in vitro cytotoxicity experiments showed that with the increase of the carbon chain(8-16 C)at both ends of bipyridine,the cytotoxicity first increased and then decreased.When the compound with 13 saturated carbon chains at both ends of bipyridine showed the best cytostatic activity against all tested human cancer cells and cisplatin-resistant A549 cancer cells in vitro,its IC₅₀ value was in the low micromolar range,even excellent than cisplatin.In addition,compound 6 blocks the cell cycle in G2/M phase.Finally,compound 6may induce cell apoptosis through membrane damage.This provided important experimental data for the future structural optimization and research of bipyridinium compounds.Subsequently,this article studied the efficiency of a series of iron compounds to generate·OH(hydroxyl radicals)through the Fenton reaction,and found that ferrocenecarboxylic acid(FCA)has the best catalytic activity for·OH formation.Then,this paper designed and prepared a NIR(near infrared)response to folic acid targeting nanomicelles,which co-deliver FCA,cisplatin,and indocyanine green(indocyanine green,ICG)to achieve enhanced oxidation response Stimulates anti-tumor therapy.Under the irradiation of near-infrared light,the lecithin structure can be depolymerized by the photothermal conversion mechanism of the encapsulated ICG,so as to realized the intelligent release of the drug.In vitro cytotoxicity experiments showed that due to synergistic oxidative damage,ICG/Pt/FCA@NPs nanoparticles loaded with FCA exhibited higher cytotoxicity than unloaded ICG/Pt@NPs.It is expected that this intelligently responsive drug delivery nanosystem can provided new guiding ideas for platinum drug anti-tumor therapy.Finally,this article synthesized cationic polymer MV-PAH[viologen-Poly(allylamine hydrochoride)],and then effectively constructed a new pH-responsive nanocarrier based on biocompatible Fe-MOF(metal-organic framework)for carrying Fe-MOF system modified by cationic polymer MV-PAH multilayerfilm prepared by layer-by-layer self-assembly(LBL)technology.In the weakly acidic environment of tumor cells,PEM(polymer electrolyte membrane)can effectively control the release of drugs,greatly enhancing the delivery of drugs.In cytotoxicity and apoptosis experiments,DOX@Fe-MOF@PEM significantly inhibited cancer cells.DOX(doxorubicin)and MV-PAH induced H2O2 can catalyzed the formation of toxic hydroxyl radicals from iron ions in cells through Fenton-like reactions,and enhance the anti-cancer effect of DOX.This novel strategy created a potential way to provide the synergistic effect of ROS and find a suitable chemotherapy regimen that can enhance anti-cancer efficacy.The relevant experimental results provided important experimental data for further research in the structure optimization of bipyridinium ion compounds and the application in nano-delivery systems.