Graphene-Nanoparticle-Based Self-Healing Hydrogel in Preventing Postoperative Recurrence of Breast Cancer.

Abstract

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.