多巴胺改性水凝胶荷载顺铂抑制KRAS突变肺癌细胞增殖的研究

Dopamine-modified hydrogels loaded with cisplatin inhibit the proliferation of KRAS mutant lung cancer cells

目的:观察荷载顺铂的多巴胺改性水凝胶对KRAS突变肺癌细胞增殖的影响。方法:以聚乙烯吡咯烷酮(PVP)与壳聚糖为材料合成注射用水凝胶,化学交联法引入多巴胺形成多巴胺改性水凝胶;细胞共培养研究多巴胺改性水凝胶的溶胀性、生物安全性及载药释放能力;体外共培养研究多巴胺改性水凝胶荷载顺铂对KRAS突变肺癌细胞增殖的影响;裸鼠体内异种移植瘤研究多巴胺改性水凝胶荷载顺铂对移植瘤增殖的抑制作用。结果:多巴胺改性水凝胶具有很强的溶胀性、良好的生物安全性、强大的药物荷载释放能力及敏感的pH组织环境识别力,多巴胺改性水凝胶荷载顺铂给药较单独顺铂给药对体内外KRAS突变肺癌细胞的增殖均具有更强的抑制作用。结论:传统细胞毒药物与多巴胺改性水凝胶结合具有更强的抗肿瘤作用,可能为将来细胞毒药物抗肿瘤治疗提供新的给药模式。

Objective:To investigate the effect of dopamine-modified hydrogel loaded with cisplatin on the proliferation of KRAS mutant lung cancer cells.Methods:Polyvinylpyrrolidone(PVP)and chitosan were used to synthesize hydrogel for injection,and dopamine was introduced to form modified hydrogel by chemical crosslinking method.The swelling,biosafety and drug-carrying capacity of dopamine-modified hydrogel were studied by cell co-culture.The effect of dopamine-modified hydrogel loaded with cisplatin on the proliferation of KRAS mutant lung cancer cells was studied in vitro co-culture.The inhibitory effect of dopamine-modified hydrogel loaded with cisplatin on the proliferation of xenografted tumor in nude mice was studied.Results:The dopamine-modified hydrogel has strong swelling property,good biosafety,strong drug load and release ability and sensitive pH tissue environment recognition ability.The dopamine-modified hydrogel loaded with cisplatin has a stronger inhibitory effect on the proliferation of KRAS mutant lung cancer cells in vitro and in vivo than that of cisplatin alone.Conclusion:The combination of traditional chemotherapy drugs and dopamine-modified hydrogels has stronger anti-tumor effect,which may provide a new solution for anti-tumor therapy in the future.