Yang Peng, Luo Xianfu, Wang Sheng, Wang Fang, Tang Chuanbing, Wang Changchun
State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, and Laboratory of Advanced Materials, Fudan University, Shanghai, 200433, People's Republic of China; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208, United States.
Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025, China.
Colloids Surf B Biointerfaces. 2017 Mar 1;151:333-343. doi: 10.1016/j.colsurfb.2016.12.037. Epub 2016 Dec 26.
A new class of uniform biodegradable yolk-shell FeO@PFH@PMAA-DOX microspheres was developed as ultrasound/MR dual-modality imaging contrast agents and drug delivery system. PMAA shells exhibit excellent drug loading capability and efficiency, the DOX-loading capacity is 15.4wt% and the drug loading efficiency is 91%. In vivo ultrasound and MRI experiments indicate that the as-prepared FeO@PFH@PMAA-DOX microspheres successfully reach tumor tissues and possess robust dual-modality imaging capability, the r value of MRI is 71.82mMs. In vitro cytotoxicity and in vivo tissues biopsies show that the loaded DOX can be control-released under pH, redox and ultrasound multi-stimuli and kill cancer cells effectively. Furthermore, disulfide-crosslinked PMAA shells and PGA-stabilized FeO cores can be respectively degraded into short hydrophilic polymer chains and iron ions, reducing their cumulative toxicity in organisms. Thus, the multifunctional biodegradable microspheres are safer for normal tissues and more beneficial in actual clinical applications.
一类新型的均匀可生物降解的蛋黄壳结构FeO@PFH@PMAA-DOX微球被开发用作超声/磁共振双模态成像造影剂和药物递送系统。聚甲基丙烯酸(PMAA)壳表现出优异的载药能力和效率,阿霉素(DOX)负载量为15.4wt%,载药效率为91%。体内超声和磁共振成像实验表明,所制备的FeO@PFH@PMAA-DOX微球成功到达肿瘤组织并具有强大的双模态成像能力,磁共振成像的r值为71.82mMs。体外细胞毒性和体内组织活检表明,负载的DOX可在pH、氧化还原和超声多刺激下实现可控释放,并有效杀死癌细胞。此外,二硫键交联的PMAA壳和聚谷氨酸(PGA)稳定的FeO核可分别降解为短的亲水性聚合物链和铁离子,降低它们在生物体内的累积毒性。因此,这种多功能可生物降解微球对正常组织更安全,在实际临床应用中更有益。