Univ Angers, Inserm, CNRS, MINT, SFR ICAT, F-49000 Angers, France.
Univ Louvain, LDRI, ADDB, Brussels, Belgium.
Biomater Adv. 2023 Oct;153:213549. doi: 10.1016/j.bioadv.2023.213549. Epub 2023 Jul 4.
The objective of this work was to develop an implantable therapeutic hydrogel that will ensure continuity in treatment between surgery and radiochemotherapy for patients with glioblastoma (GBM). A hydrogel of self-associated gemcitabine-loaded lipid nanocapsules (LNC) has shown therapeutic efficacy in vivo in murine GBM resection models. To improve the targeting of GBM cells, the NFL-TBS.40-63 peptide (NFL), was associated with LNC. The LNC-based hydrogels were formulated with the NFL. The peptide was totally and instantaneously adsorbed at the LNC surface, without modifying the hydrogel mechanical properties, and remained adsorbed to the LNC surface after the hydrogel dissolution. In vitro studies on GBM cell lines showed a faster internalization of the LNC and enhanced cytotoxicity, in the presence of NFL. Finally, in vivo studies in the murine GBM resection model proved that the gemcitabine-loaded LNC with adsorbed NFL could target the non-resected GBM cells and significantly delay or even inhibit the apparition of recurrences.
这项工作的目的是开发一种可植入的治疗性水凝胶，以确保胶质母细胞瘤（GBM）患者在手术和放化疗之间的治疗连续性。自组装的载有吉西他滨的脂质纳米囊（LNC）水凝胶在小鼠 GBM 切除模型中显示出了体内治疗效果。为了提高 GBM 细胞的靶向性，将 NFL-TBS.40-63 肽（NFL）与 LNC 结合。基于 LNC 的水凝胶与 NFL 一起被配制。肽完全且瞬时地被吸附在 LNC 表面，不会改变水凝胶的机械性能，并且在水凝胶溶解后仍吸附在 LNC 表面。对 GBM 细胞系的体外研究表明，在存在 NFL 的情况下，LNC 的内化速度更快，细胞毒性增强。最后，在小鼠 GBM 切除模型中的体内研究证明，负载有吸附 NFL 的吉西他滨的 LNC 可以靶向非切除的 GBM 细胞，并显著延迟甚至抑制复发的出现。
