Louvain Drug Research Institute, Advanced Drug Delivery & Biomaterials, Université Catholique de Louvain, Avenue Mounier, 1200 Brussels, Belgium.
Micro & Nanomédecines Translationnelles-MINT, UNIV Angers, INSERM U1066, CNRS UMR 6021, UBL Université Bretagne Loire, Angers, France.
Nanomedicine (Lond). 2018 Aug;13(16):1999-2013. doi: 10.2217/nnm-2018-0057. Epub 2018 Sep 11.
Anticancer drug-loaded hydrogels are a promising strategy for the local treatment of incurable brain tumors such as glioblastoma (GBM). Recently, we demonstrated the efficacy of lauroyl-gemcitabine lipid nanocapsule hydrogel (GemC-LNC) in a U-87 MG xenograft orthotopic mouse model. In this study, we developed a reliable and reproducible surgical procedure to resect orthotopic GBM tumors in rats. GemC-LNC hydrogel integrity was tested after brain administration in rats and its anti-tumor efficacy was tested on a 9L syngeneic orthotopic model.
We demonstrated that LNC integrity is maintained at least for one week after local administration of GemC-LNC. GemC-LNC was able to delay the formation of recurrences in 9L tumor-bearing resected rats, demonstrating the efficacy of this nanomedicine hydrogel in this preclinical model.
Our results confirm that GemC-LNC, a hydrogel uniquely formed by a nanocarrier and a cytotoxic drug, could be a promising and safe delivery tool for the local treatment of operable GBM tumors.
载抗癌药物的水凝胶是治疗复发性脑肿瘤（如胶质母细胞瘤（GBM））的一种很有前途的局部治疗策略。最近，我们在 U-87 MG 异种移植原位小鼠模型中证明了 lauroyl-吉西他滨脂质纳米囊泡水凝胶（GemC-LNC）的疗效。在这项研究中，我们开发了一种可靠且可重复的手术程序，用于切除大鼠的原位 GBM 肿瘤。在大鼠脑内给药后测试了 GemC-LNC 水凝胶的完整性，并在 9L 同源原位模型上测试了其抗肿瘤功效。
我们证明，GemC-LNC 的 LNC 完整性在局部给予 GemC-LNC 后至少可以维持一周。GemC-LNC 能够延迟接受切除的 9L 荷瘤大鼠复发的形成，证明了这种纳米医学水凝胶在该临床前模型中的疗效。
我们的结果证实，GemC-LNC 是一种由纳米载体和细胞毒性药物独特形成的水凝胶，可能是治疗可手术 GBM 肿瘤的一种有前途且安全的局部治疗工具。
