State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou Road, Nanjing 210096, P. R. China.
Nanoscale. 2018 Jan 25;10(4):2115-2127. doi: 10.1039/c7nr07495f.
Developing biocompatible and photodegradable photothermal agents (PTAs) holds great promise for potential clinical applications in photothermal cancer therapy. Herein, a new PTA was innovatively constructed by conjugating the hydrophobic near-infrared (NIR) heptamethine cyanine molecule IR825-NH with a double hydrophilic block copolymer methoxypoly(ethylene glycol)-block-poly(l-aspartic acid sodium salt) (abbreviated as PEG-PLD) via amine-carboxyl reaction. The as-designed PEG-PLD(IR825) was amphiphilic and could self-assemble into polymeric nanomicelles in aqueous solutions. Benefiting from the chemical conjugation strategy, PEG-PLD(IR825) nanomicelles realized a considerably high drug loading rate (∼21.0%) and substantially avoided the premature release of IR825 during systemic circulation. Confocal imaging revealed that the nanomicelles mainly located at mitochondria and endoplasmic reticulum after cellular internalization. In vitro photothermal therapy demonstrated the excellent cancer killing efficiency of PEG-PLD(IR825) nanomicelles due to their high light-to-heat conversion efficiency upon NIR laser irradiation. In addition, PEG-PLD(IR825) nanomicelles showed polarity-sensitive fluorescence at ∼610 nm (under 552 nm excitation) and 830 nm (under 780 nm excitation), which was especially useful for both in vitro visible fluorescence imaging and in vivo near-infrared fluorescence imaging-guided photothermal therapy (PTT). At the in vivo level, PEG-PLD(IR825) nanomicelles exhibited an excellent tumor-homing ability and a long retention time in tumor tissues as evidenced by the in vivo fluorescence imaging results. The desirable properties of PEG-PLD(IR825) nanomicelles ensured their effective tumor ablation during PTT treatment. More importantly, the PEG-PLD(IR825) nanomicelles underwent degradation after laser irradiation, which ensured their post-treatment biosafety. Therefore, the nanomicelles are promising to serve as an efficient and safe PTA for imaging-guided photothermal cancer therapy.
构建具有良好生物相容性和光降解性的光热试剂（PTAs）在光热癌症治疗的潜在临床应用中具有广阔的前景。在此，通过胺-羧基反应，将疏水性近红外（NIR）七甲川菁染料 IR825-NH 与双亲水嵌段共聚物甲氧基聚乙二醇-聚（L-天冬氨酸钠盐）（简称 PEG-PLD）偶联，创新性地构建了一种新型 PTA。设计的 PEG-PLD（IR825）具有两亲性，可在水溶液中自组装成聚合物纳米胶束。受益于化学偶联策略，PEG-PLD（IR825）纳米胶束实现了相当高的药物载药量（约 21.0%），并在体循环过程中大大避免了 IR825 的过早释放。共聚焦成像显示，纳米胶束在细胞内化后主要定位于线粒体和内质网。体外光热治疗结果表明，PEG-PLD（IR825）纳米胶束由于其在近红外激光照射下的高光热转换效率，具有优异的癌症杀伤效率。此外，PEG-PLD（IR825）纳米胶束在约 610nm（552nm 激发下）和 830nm（780nm 激发下）处表现出极性敏感的荧光，这对于体外可见荧光成像和体内近红外荧光成像引导的光热治疗（PTT）特别有用。在体内水平，PEG-PLD（IR825）纳米胶束表现出优异的肿瘤归巢能力和在肿瘤组织中的长保留时间，这可以从体内荧光成像结果得到证明。PEG-PLD（IR825）纳米胶束的理想特性确保了它们在 PTT 治疗过程中的有效肿瘤消融。更重要的是，PEG-PLD（IR825）纳米胶束在激光照射后发生降解，确保了它们治疗后的生物安全性。因此，纳米胶束有望成为一种用于成像引导光热癌症治疗的高效、安全的 PTA。
