Dynamic Hybrid CB[8]-hydrogels for Delivery of Chemotherapy against Glioblastoma

胶质母细胞瘤（GB）是最具破坏性的脑肿瘤之一，占人类所有类型脑癌的50%。标准治疗包括肿瘤切除术，随后进行放疗，并同时给予替莫唑胺作为化疗药物。血脑屏障（BBB）的存在限制了大多数全身给药的化疗药物的脑渗透，并伴有外周组织毒性。可注射，自我修复和机械可调的水凝胶已经在Scherman集团内设计和开创，以匹配连续人体组织的机械特性，代表了一种新的侵袭性脑肿瘤治疗方法，克服了许多与当前最先进的治疗相关的陷阱。这些动态交联的超分子水凝胶被设计成以时空控制的方式递送化疗药物，用于治疗GB并预防肿瘤复发。对于动态混合水凝胶的开发，将采用不同的纳米颗粒制剂（中孔的、聚合的），并且随后将其封装在水凝胶基质内以定制和延长药物释放曲线。纳米颗粒的大小，载药量和它们的降解动力学将被探索，以优化这种混合制剂。将对这些混合凝胶的机械性能进行研究，并进行降解/稳定性研究，以确定最佳的纳米颗粒/凝胶比例。还将在原代GB细胞系上评价所设计凝胶的体外和体内生物相容性。

Glioblastoma (GB) is one the most devastating brain tumours accounting for 50% of all types of brain cancers in humans. Standard treatment involves tumour resection followed by radiotherapy and concomitant administration of Temozolomide as chemotherapeutic agent. The presence of the blood-brain barrier (BBB) limits the brain penetration of the majority of systemically administered chemotherapeutic drugs, accompanied by peripheral tissue toxicity. Injectable, self-healing and mechanically tuneable hydrogels have been designed and pioneered within the Scherman group to match the mechanical properties of the contiguous human tissue, representing a new treatment methodology for aggressive brain tumours that overcome many of the pitfalls associated with the current state-of-the art treatment. These dynamically crosslinked supramolecular hydrogels are designed to deliver chemotherapeutic drugs in a spatiotemporally controlled manner for the treatment of GB and prevent tumour recurrence. For the development of dynamic hybrid hydrogels, different formulations of nanoparticles (mesoporous, polymeric) will be employed and subsequently be encapsulated within the hydrogel matrix to tailor and prolong the drug release profile. The size of nanoparticles, drug loading capacity and their degradation kinetics will be explored in order to optimise this hybrid formulation. Investigation of mechanical properties of these hybrid gels and degradation/stability studies will be performed to identify the optimal nanoparticle/gel ratio. In vitro and in vivo biocompatibility of the designed gels will also be evaluated on primary GB cell lines.