Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, The Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, China.
Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, The Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, China.
Biomaterials. 2015 Jul;57:84-92. doi: 10.1016/j.biomaterials.2015.04.001. Epub 2015 Apr 24.
The combination of chemotherapy with photothermal therapy, which may lead to improved therapeutic efficacies and reduced side effects of conventional chemotherapy, would require safe drug delivery systems (DDSs) with strong near-infrared (NIR) absorbance, efficient drug loading, and effective tumor homing ability. Herein, we fabricate nano-assemblies containing J-aggregates of a NIR dye, IR825, for drug delivery and combined photothermal & chemotherapy of cancer. It is found that IR825 could be complexed with a low-molecular-weight cationic polymer polyethylenimine (PEI), forming IR825@PEI J-aggregates with greatly enhanced NIR absorbance red-shifted to 915 nm. Those nano-assemblies of J-aggregates are further modified with polyethylene glycol (PEG), obtaining IR825@PEI-PEG nano-complex which exhibits great dispersity in physiological solutions, excellent photostability, and is able to efficiently load chemotherapeutic drug doxorubicin (DOX) via a unique strategy different from drug loading in conventional amphiphilic polymer-based DDSs. In vivo animal experiments uncover that IR825@PEI-PEG/DOX upon intravenous injection into tumor-bearing mice shows rather high tumor uptake as illustrated by photoacoustic imaging. In vivo combined photothermal & chemotherapy is then carried out, demonstrating great synergistic anti-tumor therapeutic effect remarkably superior to those achieved by the respective mono-therapies. Hence, we present a novel type of nanoscale DDSs based on nano-assemblies of small molecules without involving amphiphilic polymers, promising for imaging-guided combination cancer therapy.
化疗与光热疗法的联合应用可能会提高传统化疗的疗效，并降低其副作用，但这需要安全的药物输送系统（DDS），该系统应具有较强的近红外（NIR）吸收、高效的药物负载能力和有效的肿瘤归巢能力。在此，我们构建了包含 NIR 染料 IR825 的纳米组装体，用于药物输送和癌症的光热与化疗联合治疗。研究发现，IR825 可以与低分子量阳离子聚合物聚乙烯亚胺（PEI）复合，形成具有大大增强的 NIR 吸收的 IR825@PEI J-聚集体，其吸收峰红移至 915nm。这些 J-聚集体纳米组装体进一步用聚乙二醇（PEG）修饰，得到了 IR825@PEI-PEG 纳米复合物，该复合物在生理溶液中具有很好的分散性、优异的光稳定性，并且能够通过与传统两亲聚合物 DDS 中不同的药物负载方式高效负载化疗药物阿霉素（DOX）。体内动物实验表明，静脉注射到荷瘤小鼠体内的 IR825@PEI-PEG/DOX 通过光声成像显示出相当高的肿瘤摄取。然后进行体内联合光热与化疗，结果表明其协同抗肿瘤治疗效果明显优于单独治疗。因此，我们提出了一种基于小分子纳米组装体的新型纳米级 DDS，该 DDS 不涉及两亲聚合物，有望用于成像引导的联合癌症治疗。
