Bărăian Alexandra-Iulia, Raduly Lajos, Zănoagă Oana, Iacob Bogdan-Cezar, Barbu-Tudoran Lucian, Dinte Elena, Berindan-Neagoe Ioana, Bodoki Ede
Department of Analytical Chemistry and Instrumental Analysis, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Research Centre for Functional Genomics, Biomedicine, and Translational Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Int J Biol Macromol. 2025 Apr;298:140025. doi: 10.1016/j.ijbiomac.2025.140025. Epub 2025 Jan 17.
Glioblastoma (GBM) is a notoriously aggressive primary brain tumor characterized by elevated recurrence rates and poor overall survival despite multimodal treatment. Local treatment strategies for GBM are safer and more effective alternatives to systemic chemotherapy, directly tackling residual cancer cells in the resection cavity by circumventing the blood-brain barrier. Molecularly imprinted polymers (MIPs) are promising drug delivery systems due to their high-affinity binding cavities that enable tailored release kinetics. This study reports the development of a semi-synthetic polysaccharide MIP-based hydrogel intended for the post-surgical management of GBM. The biodegradable implant, made of calcium-crosslinked alginate-poly(N-isopropylacrylamide) graft copolymer, was designed for the sustained release of ruxolitinib (RUX) in the resection cavity, targeting the Janus kinase/Signal Transducer and Activator of Transcription-3 signaling pathway. The molecularly imprinted hydrogel demonstrated thermo-thickening and shear-thinning behavior, high entrapment efficiency of RUX (84.59 ± 0.73 %), and sustained release over 14 days, underscoring the advantages that molecular imprinting of the alginate matrix provides compared to conventional MIPs. The dose-dependent inhibitory effects of the imprinted hydrogel against U251 and A172 GBM cells were demonstrated by increased apoptosis, reduced confluence, colony formation, and delayed wound healing, whereas the non-imprinted hydrogel was biocompatible. The MIP hydrogel could be a safe and effective GBM treatment.
胶质母细胞瘤（GBM）是一种极具侵袭性的原发性脑肿瘤，其特点是尽管采用了多模式治疗，但复发率仍居高不下，总体生存率较低。GBM的局部治疗策略是全身化疗更安全、更有效的替代方案，通过绕过血脑屏障直接处理切除腔内的残留癌细胞。分子印迹聚合物（MIP）因其具有高亲和力结合腔，能够实现定制的释放动力学，是很有前景的药物递送系统。本研究报告了一种基于半合成多糖MIP的水凝胶的开发，该水凝胶旨在用于GBM的术后管理。这种由钙交联藻酸盐 - 聚（N - 异丙基丙烯酰胺）接枝共聚物制成的可生物降解植入物，设计用于在切除腔内持续释放鲁索替尼（RUX），靶向Janus激酶/信号转导子和转录激活因子3信号通路。分子印迹水凝胶表现出热增稠和剪切变稀行为，对RUX的包封效率高（84.59 ± 0.73%），并能持续释放14天，突出了藻酸盐基质分子印迹相对于传统MIP的优势。印迹水凝胶对U251和A172 GBM细胞的剂量依赖性抑制作用通过增加凋亡、降低汇合度、抑制集落形成和延迟伤口愈合得以证明，而非印迹水凝胶具有生物相容性。MIP水凝胶可能是一种安全有效的GBM治疗方法。
