多金属氧簇-聚合物复合物磁共振成像及光热-化学治疗性质  

Polyoxometalate-Polymer Composites for MR Imaging and Combined Photothermal-Chemotherapy

作　　者：周亭亭 孔雪平 万国峰 李豹[1] 吴立新[1] Ting-ting Zhou;Xue-ping Kong;Guo-feng Wan;Bao Li;Li-xin Wu(State Key Laboratory of Supramolecular Structure and Materials,College of Chemistry,Jilin University,Changchun 130012)

机构地区：[1]超分子结构与材料国家重点实验室吉林大学化学学院,长春130012

出　　处：《高分子学报》2021年第8期1032-1042,I0005,共12页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号21774050);吉林大学高层次科技创新团队(项目号2017TD-10);吉林省教育厅“十三五”科学技术项目(项目号JJKH20190116KJ)资助。

摘　　要：通过将阳离子型聚合物聚二烯丙基二甲基氯化铵、嵌段共聚物聚(甲基丙烯酸(聚乙二醇单甲醚)酯-b-甲基丙烯酸)和含Gd的多金属氧簇K_(7)(Gd(H_(2)O)_(3)P_(2)W_(17)_O(61))以及部分还原的K_(6)(α-P_(2)W_(18)O_(62))共混,构建了纳米尺寸的聚合物包埋多金属氧簇的多组分复合物PDDA-PPBM-rPOMs.实验表明,所制备的复合物在水溶液、磷酸盐缓冲液和细胞培养基溶液中都具有较好的结构稳定性,形成均一分散的直径约为67 nm的球形组装体.磁性金属氧簇的存在和较大的粒子半径使复合物在0.5 T磁场条件下的纵向弛豫效率达到51.32 L·mmol^(-1)·s^(-1),并且在载药之后没有明显降低.复合物中部分还原的多金属氧簇中的不同价态金属离子之间存在的电荷转移使复合物在载药前后均表现出良好的光热转换能力,其中,载药后的复合物在808 nm激光(1.0 W·cm^(-2))下持续照射10 min可以产生20℃的温度增量,为其用于肿瘤光热治疗提供了可能.PDDA-PPBM-rPOMs内部静电交联结构为其负载抗肿瘤药物阿霉素提供了合适的场所,使其具有超过90%的载药率,并且pH=5.0下的累积释药量是pH=7.4下的3倍,表现出明显的pH响应性药物释放能力.细胞毒性和流式细胞凋亡实验表明载药的复合物在激光照射下可以有效地抑制肿瘤细胞生长,实现光热治疗与化学治疗的协同,这也为多金属氧簇多功能复合材料用于肿瘤诊断和治疗一体化的发展提供了可用思路.This work reports a nano-sized multicomponent composite of cationic poly(diallyldimethylammonium chloride)incorporating with ionic components of biocompatible block copolymer poly(poly(ethylene glycol)methyl ether methacrylate-b-methacrylic acid)(PPBM),gadolinium-coordinated polyoxometalate cluster K7(Gd(H_(2)O)_(3)P_(2)W_(17)O_(61))and K_(6)(α-P_(2)W_(18)O_(62))at the reduction state,as a polymer-covered theranostic nanoplatform for MRI-guided chemo-photothermal combination tumor therapy.The as-prepared composites PDDA-PPBM-rPOMs with a hydrodynamic diameter of 67 nm show good structural stability and biocompatibility against HeLa cells.The internal electrostatic crosslinking structure and the surplus negative charges of the polymers/polyoxometalates composites facilitated the loading of antitumor drug doxorubicin(DOX).The PDDA-PPBM-rPOMs composites before and after drug loading both possess enhanced MRI efficacy as MRI contrast agents with high longitudinal relaxivities up to about 50 L·mmol^(-1)·s^(-1).With the aid of reduced K6(α-P_(2)W_(18)O_(62))as photothermal therapy agent,the DOX loaded composites displayed unique photothermal conversion capacity.Meanwhile,the DOX loaded in the composite exhibited significant pH responsive drug release behavior.Cytotoxicity and flow cytometric apoptosis experiments showed that the drug-loaded composite can effectively inhibit tumor cell growth and achieve a photothermal-chemical synergistic therapeutic effect under laser irradiation,which provided a new strategy for the further development of polyoxometalate-based multifunctional composite for the integration of tumor diagnosis and treatment.

关 键 词：磁共振成像 光热-化学联合治疗 聚合物 多金属氧簇 药物释放 

分 类 号：TB332[一般工业技术—材料科学与工程] TQ460.4[化学工程—制药化工] R730.5[医药卫生—肿瘤]