Design and development of metal-organic frameworks for the delivery of mRNA

癌症是世界范围内的主要健康问题，是仅次于心血管疾病的最常见死亡原因。新的抗癌疗法的主要目标是在不伤害健康细胞的情况下特异性地杀死肿瘤细胞。实现这一目标的主要挑战是开发更好的治疗方法，包括基于使用能够干扰细胞信号系统的分子（如mrna）的新治疗方法。这些大分子可能是目前存在的最强大的抗癌药物，然而，尽管这些疗法具有突出的潜力，mrna的生物稳定性极低，不能在体内给药。在纳米医学和药物递送中，封装mRNA以保护和递送的可能性是最大的挑战之一。本研究的目的是利用金属有机框架（mof），一种独特的多孔混合固体材料，作为癌症治疗的药物输送系统。mof结合了巨大的结构和化学多样性，这使得它们对于包封（即在其内部多孔表面吸附）和释放治疗剂非常有吸引力，这要归功于它们与化学基团的功能化，控制治疗剂的动力学释放的可能性。该项目的成功将导致基于mof的创新癌症治疗系统的实现，该系统可用于体内研究，并对许多患者的生命有好处。

Cancer is a major health problem worldwide being the most common cause of death after cardiovascular diseases. The major goal of new anticancer therapies is to specifically kill tumour cells while leaving healthy cells unharmed. A mainchallenge to achieve this aim is the development of better therapies, including novel treatments based on the use of molecules capable of interfere the cell signalling system such as mRNAs. These macromolecules are potentially themost powerful anti-cancer drugs that exist, however, despite of the outstanding potential of these therapies, mRNAs biostability is extremely low and cannot be administered in vivo. The possibility of encapsulating mRNA for their protectionand delivery is one of the greatest challenges in nanomedicine and drug delivery. The aim of this research is to use Metal-Organic Frameworks (MOFs), a unique class of porous hybrid solid materials, as a drug delivery system for cancertherapy. MOFs combine vast structural and chemical diversity that make them extremely attractive for the encapsulation (i.e. adsorption in their internal porous surface) and release of therapeutic agents, thanks to the possibility tofunctionalize them with chemical groups, controlling the kinetic release of a therapeutic agent. The success of this project will lead to the realization of innovative MOF-based systems for cancer therapy which can then be used for in vivostudies and have a benefits on the life of numerous patients.