Construction Of Nanometer Cisplatin Core-Ferritin And Expression Level Of H And M Subunits Of Fish (Danio Rerio)Ferritin Exposed To Iron

Massive researches have reported there is one kind of protein called ferritin existed in animals, plants and microorganisms which could store iron for multiple vital processes. Ferritin molecular structure consists of protein capsid, iron micelle and multiple tunnels. For the past few years, there have been plentiful researches about construction of nanometer drug core-ferritin, but seldom about nanometer cisplatin core-ferritin. At present, the cisplatin and carboplatin are the main antineoplastic drugs with the broad clinical spectrum, but they have vastly clinical dose limitation by their severe renal toxicity and drug resistence. So the impending challenge has been put out on how to elevate the pharmaceutical effect, reduce the toxicity and avoid the resistence.Aiming at the pharmaceutical flaw of platinum antineoplastic drugs illustrated above, this study addressed the biochemical characteristics of Danio rerio ferritin H and M subunits (no L chain found in zebrafish) and epressional levels in six organs, and we constructed a protein drug delivery system using rDRFerritin packaging multiple platinum anti-cancer drugs. The data showed that rDRFerritin could package at most43CDDP molecules in one protein almost without outer surface binding (Concentration Mean±SD=0.064μg/L, Molecular Ratio (Pt:rDRH)=0.0174:1), and induce more Hep G Ⅱ apoptosis (23.5%) than in the positive control (13.9%). The nanometer cisplatin core-ferritin could effectively elevate the pharmaceutical effect than the free cisplatin, meanwhile reduce the toxicity.We also measured each subunit mRNA level in the brain, gill, liver, intestine, muscle and egg (which actually is ovarian follicle) of the both genders of D. rerio under natural and ferric (0.3,1.0,5,10and20mg/L) or ferrous (0.3,1.0,2.5and5.0mg/L) ion threatening circumstances for24h. The experiment aimed at the relationships between the iron element and the subunits’expression levels using zebrafish as animal model, had provided significant scientific basis for elaboration of the ferritin-iron metabolism.