Chiral Drug Delivery Systems to Tackle Cancerous Chirality

材料科学领域多年来塑造了人类的历史，药物输送系统带来了受控的、时间敏感的药物释放机制的开始。手性是天然物质普遍存在的一种性质，也被认为是药物的一种基本物理化学性质。在药物递送系统(DDS)中，这一方面到目前为止被忽视了，但要开发出高效和特定的系统，手性必须被考虑。该项目致力于设计和开发针对癌细胞特有的肿瘤手性和拓扑变化的新型手性DDS。为了设计这些系统，需要探索和表征健康细胞和癌细胞的手性和拓扑结构，包括肿瘤的形成过程。DDS的合成将解决肿瘤特定的手性靶点以及癌细胞的独特拓扑结构。利用聚(乳酸-乙醇酸)和聚甘油聚蓖麻油酸酯共聚物的微尺度结构，或使用钛(IV)基络合物来获得金属螺旋体系，可以实现对癌细胞的整体靶向。纳米级的传递系统将在非手性聚合物主干中引入手性分子，从而控制整体的利手性。总体而言，拟议的项目立志于设计和制造开创性的手性递送系统，以实现卓越的靶向性和特异性，从而实现安全和高效的给药。

Material science field has shaped the history of humankind for ages with drug delivery systems bringing the inception of controlled, time sensitive release mechanism of pharmaceuticals. Chirality is a ubiquitous property of natural matter and was also introduced as an essential physiochemical trait of drugs. In drug delivery systems (DDS) this aspect was overlooked so far but to develop highly efficient and specific systems, chirality must be considered. The proposed project strives to design and develop novel chiral DDS targeting the neoplastic chiral and topological changes uniquely exhibited by cancer cells. To design these systems, chirality and topology of healthy and cancer cells need to be explored and characterized, including the tumour formation process. Synthesis of DDS will address the tumour specific chiral targets as well as the unique topology of the cancer cells. Targeting cancer cells as a whole would be achieved using poly(lactic-co-glycolic acid) and polyglycerol polyricinoleate copolymers micro sized structures, or using Ti(IV) based complexes to obtain metallohelical systems. Nano- size delivery systems will incorporate chiral molecules within achiral polymer backbone, controlling the overall handedness. Overall, the proposed project aspires to design and fabricate pioneering chiral delivery systems to achieve superior targeting and specificity to achieve safe and efficient drug administration.