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。新抗癌疗法的主要目标是特异性杀死肿瘤细胞，同时使健康细胞不受伤害。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，但mRNA的生物稳定性极低，不能在体内施用。包裹mRNA以保护和递送mRNA的可能性是纳米医学和药物递送中最大的挑战之一。本研究的目的是利用金属-有机骨架（MOFs），一类独特的多孔杂化固体材料，作为癌症治疗的药物递送系统。MOFs联合收割机结合了巨大的结构和化学多样性，这使得它们对于治疗剂的包封（即在其内部多孔表面中的吸附）和释放极具吸引力，这归因于用化学基团使它们官能化的可能性，从而控制治疗剂的动力学释放。该项目的成功将导致实现基于MOF的创新癌症治疗系统，然后可用于体内研究，并对许多患者的生活产生益处。

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.