Dual-sensitive drug-loaded hydrogel system for local inhibition of post-surgical glioma recurrence

• Published in: Journal of controlled release 2022-09, Vol.349, p.565-579
• Main Authors: Chen, Sunhui, Qiu, Qiujun, Wang, Dongdong, She, Dejun, Yin, Bo, Gu, Guolong, Chai, Meihong, Heo, Dong Nyoung, He, Huining, Wang, Jianxin
• Format: Article
• Language: English
• Subjects: Glioma recurrence; Magnetic resonance imaging; Reactive oxygen species-sensitive nanoparticles; Synergistic effect; Thermo-sensitive hydrogel
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2022.07.011

Local treatment after resection to inhibit glioma recurrence is thought to able to meet the real medical needs. However, the only clinically approved local glioma treatment-wafer containing bis(2-chloroethyl) nitrosourea (BCNU) showed very limited effects. Herein, in order to inhibit tumor recurrence with prolonged and synergistic therapeutic effect of drugs after tumor resection, an in situ dual-sensitive hydrogel drug delivery system loaded with two synergistic chemo-drugs BCNU and temozolomide (TMZ) was developed. The thermosensitive hydrogel was loaded with reactive oxygen species (ROS)-sensitive poly (lactic-co-glycolic) acid nanoparticles (NPs) encapsulating both BCNU and TMZ and also free BCNU and TMZ. The in vitro synergistic effect of BCNU and TMZ and in vivo presence of ROS at the residual tumor site were confirmed. The prepared ROS-sensitive NPs and thermosensitive hydrogel, as well as the long-term release behavior of drugs and NPs, were fully characterized both in vitro and in vivo. After >90% glioblastoma resection, the dual-sensitive hydrogel drug delivery system was injected into the resection cavity. The median survival time of the experimental group reached 65 days which was twice as long as the Resection only group, implying that this in situ drug delivery system effectively inhibited tumor recurrence. Overall, this study provides new ideas and strategies for the inhibition of postoperative glioma recurrence. An in situ dual-responsive hydrogel drug delivery system was prepared to inhibit the glioma recurrence with prolonged and synergistic therapeutic effect of drugs after surgical resection. [Display omitted] •An in situ dual-sensitive hydrogel system to inhibit GBM recurrence with prolonged and synergistic effect post-resection.•A “two-phase drug release” was to fast kill most of residual GBM cells and sustainingly inhibit the rest of GBM cells.•Median survival time of experimental group reached 65 days, implying this system can effectively inhibit GBM recurrence.