摘要
利用油胺和赖氨酸铜共修饰的聚琥珀酰亚胺两亲高分子(PSI_(Lys-Cu-Lys/OAm)),实现对全氟冠醚(PFCE,作为氟源)、阿霉素(DOX)的自组装包封,并进一步通过聚赖氨酸(PLL)调节表面静电作用负载葡萄糖氧化酶(GOx),获得DOX/F@PSI_(Lys-Cu-Lys/OAm)@PLL-GOx(DFPPG)多功能纳米探针,成功将^(19)F磁共振成像(MRI)引导的化学动力学(CDT)/饥饿(ST)/化疗(CT)联合治疗整合于一个纳米平台。体外及活体实验结果表明,探针基于类GOx酶活性有效地催化消耗细胞内葡萄糖转化为H_(2)O_(2)和葡萄糖酸,不仅可以“饿死”肿瘤,而且原位自供应H_(2)O_(2)及酸性增强进一步促进了Cu介导的类芬顿反应,增强了CDT。与此同时,探针在肿瘤微酸性环境下响应性释放DOX,解决了化疗药物的生物利用率低问题且降低了探针对正常组织的毒副作用,优异的^(19)FMRI实现了探针(药物)代谢过程的示踪。
The copper lysine and oleylamine-modified polysuccinimide amphiphilic molecule(PSI_(Lys-Cu-Lys/OAm))were used to encapsulate and assemble perfluorocarboxane(PFCE,as the fluorine source)and doxorubicin(DOX).Further,glucose oxidase(GOx)was loaded onto the nanoprobes by regulating surface electrostatic interactions using polylysine(PLL).This led to the development of multifunctional nanoprobes,termed DOX/F@PSI_(Lys-Cu-Lys/OAm)@PLL-GOx(DFPPG),integrating ^(19)F magnetic resonance imaging(MRI)-guided chemodynamic,starvation,and chemotherapy into a unified nanoplatform.Both in vitro and in vivo experiments showed that the nanoprobes effectively catalyzed intracellular glucose to generate H_(2)O_(2)and gluconic acid based on GOx-like activity.This not only induced tumor“starvation”but also facilitated the Cu-mediated Fenton-like reaction,enhancing chemodynamic therapy(CDT)by in-situ self-supply of H_(2)O_(2)and acidic enhancement.Simultaneously,the as-prepared nanoprobe released DOX in response to the slightly acidic tumor environment,addressing the challenge of low bioavailability of chemotherapy drugs and reduced the toxic side effects of the probe on normal tissues.The excellent^(19)FMRI realized the tracing of the metabolic process of the probe(drug).
作者
刘晓彤
马景晶
胡高飞
LIU Xiao-tong;MA Jing-jing;HU Gao-fei(College of Chemistry,Beijing University of Chemical Technology,Beijing 100029,China)
出处
《化学试剂》
CAS
2024年第2期28-38,共11页
Chemical Reagents
基金
国家自然科学基金面上项目(22076010)
国家重点研发计划子课题项目(2019YFC1906104)。
