The Development Of Fe₃O₄-CS-BCG Complexes And Study Of The Anti-tumor Effects On Bladder Cancer

Objective:To prepare a new nano-ferrite,BCG and chitosan complexes, build a BCG targeting adhesion release system, examine its characterization, bladder distribution, long-term biological toxicity and study its anti-tumor effects, then evaluate its synergies of BCG in bladder.Methods:1.Construction of the Fe3O4-CS-BCG complexes:Using chitosan as a carrier of BCG, the nano-ferrite, chitosan and BCG were combined to form the BCG targeting adhesion release system.The characterization of the complexes were confirmed by IR,XRD,SEM,TEM and VSM.2.Detection of biological activity of Fe3O4-CS-BCG complexes: Under the intension of magnet, frozen sections were used to verify the adhesion complex targeting in the rat bladder; Local immune activity in the bladder was evaluated by IL-2; The systemic toxicity was observed through long-term applications.3. Anti-tumor effect of the complexes:Establish a rat bladder cancer model. Fe3O4-CS-BCG complexes were perfused into bladder to antagonize the tumor. The anti-tumor effect was assess by urine testing, HE staining, immunohistochemical staining, apoptosis detection.Results:1. Fe3O4-CS-BCG complexes were grayish black and gelatinous. Under the electron microscopy, BCG and Fe3O4resides in the chitosan mesh-like structure. The complex still has a magnetic response.2. Observed from the frozen section, the complexes and the bladder wall combined close in the magnetic field. The retention time of complexes was up to72hours, several times than the ordinary BCG. Compared with ordinary BCG,intravesical immune inflammatory response of the complexes is stronger.Rat liver and kidney function, blood routine index showed no significant abnormality; heart, kidney and pathological examination showed no significant pathological damage, which proved that the systemic toxic reaction is weak.3.Urine concentration of TRAIL were obviously higher than normal BCG. The induced tumor grading and proliferative degree is low, and the rate of tumor apoptosis is high. The experimental results are basically consistent. Fe3O4-CS-BCG complexes has stronger antitumor activity than ordinary BCG.Conclusion:We successfully prepared Fe3O4-CS-BCG complexes., It is stable and has superparamagnetic. Under an external magnetic field, it produces obvious targeting adhesion in rat bladder up to72hours. It produces stronger immune function in the bladder than ordinary BCG.The systemic toxicity is weak.The anti-tumor effect is better than that of ordinary BCG. We find that the Fe3O4-CS-BCG complexes enhanced BCG immunization activity and anti-tumor effect. It is expected to be used for bladder carcinoma to prevent recurrence of bladder carcinoma with wide clinical application prospect.