Li Qiwen, Wen Junru, Liu Chenlu, Jia Yanpeng, Wu Yongzhi, Shan Yue, Qian Zhiyong, Liao Jinfeng
ACS Biomater Sci Eng. 2019 Feb 11;5(2):768-779. doi: 10.1021/acsbiomaterials.8b01475. Epub 2019 Jan 28.
Hydrogel is an ideal scaffold in the fields of regenerative medicine and tumor therapy because of its biomimetic ability to modulate tissue microenvironment. Herein, we fabricated a new kind of self-healing hydrogel based on graphene nanoparticle and expanded its application in postoperative recurrence of breast cancer. First, a facile method was used to prepare self-healing hydrogel via Schiff-base linkage, which composed of chondroitin sulfate multialdehyde (CSMA), branched polyethylenimine (BPEI) and BPEI conjugated graphene (BPEI-GO). BPEI-GO was doped in the network and participated in Schiff-base reaction and stabilized the structure, as well as provided sustained drug delivery, and near-infrared laser (NIR)-triggered photothermal effect. The hydrogels exhibited excellent self-healing (∼100%) and improved mechanical properties (7,000 Pa). Further, in vitro breast cancer cell inhibition study showed enhanced cell killing efficiency with synergistic chemo-photothermal therapy. In the breast cancer postoperative recurrence prevention mice model, we found that combination of Doxorubicin (DOX) and photothermal therapy in CSMA/BPEI/BPEI-GO hydrogels group reduced tumor recurrence to 33.3%, compared with 66.7% for DOX-loaded hydrogels without NIR irradiation, 66.7% for local administration of free DOX, 100% for hydrogels with NIR irradiation, blank hydrogels, and blank control. This study suggests the great potential of CSMA/BPEI/BPEI-GO hydrogels for postoperative recurrence prevention of breast cancer.
水凝胶因其具有调节组织微环境的仿生能力，是再生医学和肿瘤治疗领域理想的支架材料。在此，我们制备了一种基于石墨烯纳米颗粒的新型自愈合水凝胶，并拓展了其在乳腺癌术后复发治疗中的应用。首先，采用一种简便的方法通过席夫碱连接制备自愈合水凝胶，该水凝胶由硫酸软骨素多醛（CSMA）、支化聚乙烯亚胺（BPEI）和BPEI共轭石墨烯（BPEI-GO）组成。BPEI-GO掺杂在网络中，参与席夫碱反应并稳定结构，同时提供持续的药物递送以及近红外激光（NIR）触发的光热效应。该水凝胶表现出优异的自愈合性能（约100%）和改善的力学性能（7000 Pa）。此外，体外乳腺癌细胞抑制研究表明，协同化疗-光热疗法可提高细胞杀伤效率。在乳腺癌术后复发预防小鼠模型中，我们发现，与未进行NIR照射的载有多柔比星（DOX）的水凝胶组复发率为66.7%、局部注射游离DOX复发率为66.7%、进行NIR照射的水凝胶组复发率为100%、空白水凝胶组及空白对照组相比，CSMA/BPEI/BPEI-GO水凝胶组中DOX与光热疗法联合使用可将肿瘤复发率降低至33.3%。这项研究表明CSMA/BPEI/BPEI-GO水凝胶在预防乳腺癌术后复发方面具有巨大潜力。
