期刊
JOURNAL OF CONTROLLED RELEASE
卷 349, 期 -, 页码 565-579出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2022.07.011
关键词
Glioma recurrence; Reactive oxygen species -sensitive nanoparticles; Synergistic effect; Thermo -sensitive hydrogel; Magnetic resonance imaging
资金
- National Natural Science Foundation of China [82074277, 8177391, 82173769]
- National Key Research and Development Program of China [2021YFE0106900]
- Basic Research Cooperation Project of Beijing, Tianjin, Hebei from Natural Science Foundation of Tianjin [J200018, 20JCZXJC00070]
- Development Project of Shanghai Peak Disciplines -Integrated Medicine [20180101]
A dual-sensitive hydrogel drug delivery system loaded with BCNU and TMZ was developed to inhibit glioma recurrence after resection. The system effectively inhibited tumor recurrence and provided new ideas and strategies for postoperative glioma recurrence inhibition.
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.
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