NUS Graduate School of Integrative Sciences and Engineering , National University of Singapore 117456 , Singapore.
School of Life Sciences & Chemical Technology , Ngee Ann Polytechnic 599489 , Singapore.
ACS Appl Mater Interfaces. 2018 Jun 27;10(25):21125-21136. doi: 10.1021/acsami.8b04799. Epub 2018 Jun 18.
Our study shows a facile two-step method which does not require the use of core templates to load a hydrophobic photosensitizer drug chlorin e6 (Ce6) within polydopamine (PDA) nanoparticles (NPs) while maintaining the intrinsic surface properties of PDA NPs. This structure is significantly different from hollow nanocapsules which are less stiff as they do not possess a core. To our knowledge, there exist no similar studies in the literature on drug loading within the polymer matrix of PDA NPs. We characterized the drug loading and release behavior of the photosensitizer Ce6 and demonstrated the therapeutic efficacy of the combined photodynamic (PDT) and photothermal therapy (PTT) from Ce6 and PDA, respectively, under a single wavelength of 665 nm irradiation on bladder cancer cells. We obtained a saturated loading amount of 14.2 ± 0.85 μM Ce6 in 1 nM PDA NPs by incubating 1 mg/mL dopamine solution with 140 μM of Ce6 for 20 h. The PDA NPs maintained colloidal stability in biological media, whereas the pi-pi (π-π) interaction between PDA and Ce6 enabled a release profile of the photosensitizer until day 5. Interestingly, loading of Ce6 in the polymer matrix of PDA NPs significantly enhanced the cell uptake because of endocytosis. An increased cell kill was observed with the combined PDT + PTT from 1 nM PDA-Ce6 compared to that with PTT alone with 1 nM PDA and PDT alone with 15 μM equivalent concentration of free Ce6. PDA-Ce6 NPs could be a promising PDT/PTT therapeutic agent for cancer therapy.
我们的研究展示了一种简便的两步法，无需使用核模板即可在聚多巴胺（PDA）纳米粒子（NPs）内负载疏水性光敏剂药物氯乙啶 6（Ce6），同时保持 PDA NPs 的固有表面性质。这种结构与空心纳米胶囊明显不同，因为它们没有核心，所以不那么僵硬。据我们所知，目前在文献中没有关于在 PDA NPs 的聚合物基质内负载药物的类似研究。我们对光敏剂 Ce6 的负载和释放行为进行了表征，并分别在膀胱癌细胞上用 665nm 单一波长照射，展示了 Ce6 和 PDA 的光动力（PDT）和光热治疗（PTT）的治疗效果。我们通过将 1mg/mL 多巴胺溶液与 140μM 的 Ce6 孵育 20 小时，在 1nM PDA NPs 中获得了 14.2±0.85μM 的 Ce6 的饱和负载量。PDA NPs 在生物介质中保持胶体稳定性，而 PDA 和 Ce6 之间的 pi-pi（π-π）相互作用使光敏剂的释放曲线持续到第 5 天。有趣的是，由于内吞作用，Ce6 在 PDA NPs 聚合物基质中的负载显著增强了细胞摄取。与单独使用 1nM PDA 和单独使用 15μM 游离 Ce6 的 PDT 相比，1nM PDA-Ce6 的组合 PDT+PTT 观察到细胞杀伤增加。PDA-Ce6 NPs 可能是一种有前途的 PDT/PTT 治疗癌症的治疗剂。
