血红蛋白稳定的铂基聚吡咯纳米颗粒及其光热抗肿瘤研究

Hemoglobin-stabilizd platinum-based polypyrrole nanoparticles and their photothermal antitumor studies

光热治疗是利用近红外激光特异性激活蓄积在病灶部位的光热剂,从而达到热消融癌细胞的一种新型肿瘤治疗手段。然而,光热材料在体内代谢周期长、清除难,这成为阻碍其临床转化的主要障碍之一。本研究利用血红蛋白作为新型稳定剂、六氯铂酸作为新型氧化剂、吡咯作为单体,通过氧化聚合一步法,制得血红蛋白稳定的铂基聚吡咯纳米颗粒(Hb@PtP)并对其形貌结构等理化性质进行详细考察。在聚乙二醇修饰后,获得的Hb@PtPP粒径为99.08±8.3 nm,zeta电位为−18.7±1.2 mV,透射电镜显示Hb@PtPP纳米颗粒为不规则球形且分散均匀。在不同功率密度的808 nm激光照射下,Hb@PtPP呈现出功率密度依赖性升温行为,CCK-8和死活染色实验证实其能有效地发挥光热效应杀伤肿瘤细胞。小动物活体成像结果表明Hb@PtPP具有较好的肿瘤靶向和滞留能力,在激光激发下,实现了小鼠肿瘤生长的抑制和消融。研究涉及的所有动物实验均按照中国医学科学院机构动物护理与使用委员会中国医学科学院、北京协和医学院放射医学研究所批准的方案执行[IRM/2-IACUC-2312-005]。

Photothermal therapy is a new type of tumor therapy that uses near-infrared laser to specifically activate the photothermal agent accumulated in the lesion site,so as to achieve thermal ablation of cancer cells.However,the long metabolic cycle and difficult clearance of photothermal agent materials in vivo are also one of the major obstacles hindering their clinical transformation.In this work,we used hemoglobin as a novel stabilizer,hexachloroplatinic acid as a novel oxidant,and pyrrole as a monomer to prepare hemoglobin-stabilized platinumbased polypyrrole nanoparticles(Hb@PtP)by a one-step oxidative polymerization method and investigated in detail to study their physicochemical properties,such as morphology and structure.After polyethylene glycol modification,the particle size of obtained Hb@PtPP was 99.08±8.3 nm and the zeta potential was−18.7±1.2 mV.Transmission electron microscopy showed that the Hb@PtPP nanoparticles exhibited irregular spherical shape and uniform dispersion in the system.Under the irradiation of 808 nm laser with different power densities,Hb@PtPP showed power density-dependent temperature-raising behavior,and CCK-8 and dead-live staining experiments confirmed that they could effectively exert the photothermal effect to kill tumor cells.Small living animal imaging results demonstrated that Hb@PtPP had good tumor targeting and retention ability,and achieved tumor growth inhibition and ablation in vivo under laser excitation.All animal experiments involved in the study were performed in accordance with the program approved by the Animal Care and Use Committee of the Chinese Academy of Medical Sciences,Beijing Union Medical College,Institute of Radiation Medicine[IRM/2-IACUC-2312-005].