State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, 541004, P. R. China.
Biomater Sci. 2019 Aug 20;7(9):3886-3897. doi: 10.1039/c9bm00762h.
Specific targeting capabilities and effective phototherapeutic functions are the key demands for precise cancer phototherapeutic agents. Herein, a bioinspired nanoplatform composed of Cu(ii)-chlorophyll-hyaluronic acid nanoparticles (Cu(ii)Chl-HA NPs) was developed for targeting cancer and synergistic photodynamic/photothermal therapy. Inspired by the photonic biosystem of the chloroplast, Cu(ii) chlorophyll was used as a photosensitive substituent to covalently connect with a hydrophilic HA tail rather than a natural phytol tail, and this conjugate further assembled into a nanoparticle-like morphology under non-covalent interaction. Time-dependent density functional theory calculations reveal that the Cu(ii) chlorophyll has a much smaller energy gap between an excited singlet and excited triplet, and theoretically leads to rapid electron intersystem crossing that would benefit the PDT effect. In addition, a series of experiments have proven that, under 650 nm laser irradiation, the nanoplatform of Cu(ii)Chl-HA can produce a high amount of singlet oxygen and exhibit an outstanding photothermal conversion capability. More interestingly, owing to the specific interactions between the HA component and the CD44 receptor on the cell membrane, the HA tails impart Cu(ii)Chl-HA NPs an excellent receptor-mediated targeting performance toward CD44-overexpressing cancer cells. Based on these features, the nanoplatform of Cu(ii)Chl-HA NPs presents active targeting and outstanding dual modality synergistic PDT/PTT performance of cancer both in vitro and in vivo. Thus, this work opens up a new strategy to fabricate a bioinspired multifunctional cancer phototherapy nanoplatform.
特定的靶向能力和有效的光疗功能是精准癌症光疗剂的关键要求。在此，开发了一种基于仿生的纳米平台，由 Cu(ii)-叶绿素-透明质酸纳米粒子（Cu(ii)Chl-HA NPs）组成，用于靶向癌症和协同光动力/光热治疗。受叶绿体光子生物系统的启发，Cu(ii)叶绿素被用作光敏取代基，与亲水性 HA 尾巴共价连接，而不是天然植醇尾巴，并且该共轭物在非共价相互作用下进一步组装成类似纳米颗粒的形态。时变密度泛函理论计算表明，Cu(ii)叶绿素在激发单线态和激发三线态之间的能量间隙要小得多，理论上会导致快速的电子系间穿越，这将有利于 PDT 效应。此外，一系列实验已经证明，在 650nm 激光照射下，Cu(ii)Chl-HA 的纳米平台可以产生大量的单线态氧，并表现出出色的光热转换能力。更有趣的是，由于 HA 成分与细胞膜上 CD44 受体之间的特异性相互作用，HA 尾巴使 Cu(ii)Chl-HA NPs 对 CD44 过表达癌细胞具有优异的受体介导靶向性能。基于这些特点，Cu(ii)Chl-HA NPs 的纳米平台在体外和体内均表现出主动靶向和出色的双重模式协同 PDT/PTT 癌症治疗性能。因此，这项工作为构建仿生多功能癌症光疗纳米平台开辟了一条新的策略。
