Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering , Jiangnan University , Wuxi 214122 , China.
The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University , Wuxi 214002 , China.
Biomacromolecules. 2019 Sep 9;20(9):3375-3384. doi: 10.1021/acs.biomac.9b00600. Epub 2019 Aug 19.
Gold nanorods (AuNRs) are confirmed to have excellent and repeated photothermal properties under near-infrared (NIR)-light irradiation above 780 nm. However, AuNRs easily leaked out from local pathological tissues and circulated in the body, reducing photothermal therapy (PTT) efficacy. By complexing AuNRs with a scaffold via interactions, AuNRs might be dispersed in the scaffold and fixed in the tumor site. Thus, based on the mussel-mimetic adhesion concept, AuNRs were designed to be coated with polydopamine (PDA), and then the prepared polydopamine-coated AuNRs (AuNR-PDA) were incorporated into a thermosensitive injectable hydrogel composed of β-glycerophosphate-bound chitosan (CGP) and dopamine-modified alginate (Alg-DA) efficiently. Due to the strong interactions between PDA and polymers, AuNR-PDA could be immobilized stably and evenly into the obtained CGP/Alg-DA/AuNR composite hydrogel, which can avoid overheating locally or leaking out. The sol-gel transition temperature of the composite hydrogel was adjusted to the body temperature at around 37 °C to be conveniently injectable in vivo. With NIR irradiation at 808 nm of wavelength, the composite hydrogel was locally heated quickly to over 50 °C depending on controlling the irradiation powers and times. Moreover, the in vitro cytotoxicity test of the composite hydrogel showed good biocompatibility to normal cells but obvious suppression to tumor cells' growth under multiple times of photothermal therapy. Furthermore, the in vivo antitumor test demonstrated the obvious suppression to tumor growth of the CGP/Alg-DA/AuNR composite hydrogel under multiple PTTs. Therefore, the injectable CGP/Alg-DA/AuNR hydrogel could be a promising candidate for the long-term repeated photothermal treatment of tumors.
金纳米棒(AuNRs)在 780nm 以上的近红外(NIR)光照射下被证实具有优异且可重复的光热性能。然而,AuNRs 容易从局部病变组织中漏出并在体内循环,从而降低光热疗法(PTT)的疗效。通过与支架通过相互作用复合 AuNRs,AuNRs 可能会分散在支架中并固定在肿瘤部位。因此,基于贻贝类仿生黏附概念,AuNRs 被设计为涂有聚多巴胺(PDA),然后将制备的聚多巴胺涂覆的金纳米棒(AuNR-PDA)有效地掺入由β-甘油磷酸酯结合壳聚糖(CGP)和多巴胺修饰的海藻酸钠(Alg-DA)组成的温敏可注射水凝胶中。由于 PDA 和聚合物之间的强相互作用,AuNR-PDA 可以稳定且均匀地固定在所得的 CGP/Alg-DA/AuNR 复合水凝胶中,从而可以避免局部过热或泄漏。复合水凝胶的溶胶-凝胶转变温度被调整到接近 37°C 的体温,以便在体内方便地注射。在 808nm 波长的 NIR 照射下,根据控制照射功率和时间,复合水凝胶可快速局部加热至 50°C 以上。此外,复合水凝胶的体外细胞毒性试验表明,正常细胞具有良好的生物相容性,但在多次光热治疗下对肿瘤细胞的生长有明显的抑制作用。此外,体内抗肿瘤试验表明,CGP/Alg-DA/AuNR 复合水凝胶在多次 PTT 下对肿瘤生长有明显的抑制作用。因此,可注射的 CGP/Alg-DA/AuNR 水凝胶可能是肿瘤长期重复光热治疗的有前途的候选者。