Intelligent Metal Carbonyl Metal–Organic Framework Nanocomplex for Fluorescent Traceable H₂O₂‐Triggered CO Delivery

Abstract

The recognized therapeutic benefits from carbon monoxide (CO) have caused booming attention to develop a CO therapy for various major diseases, such as cancer. However, the controlled release of CO gas and the monitoring of the CO release are vitally important to the on-demand CO administration for a safe and efficient therapy, but greatly challenging. In this work, a new CO-releasing nanocomplex was constructed by the adsorption and coordination of manganese carbonyl ([MnBr(CO) ], abbreviated as MnCO) with a Ti-based metal-organic framework (Ti-MOF) to realize an intratumoral H O -triggered CO release and real-time CO release monitoring by fluorescence imaging. A high CO prodrug loading capacity (0.532 g MnCO per gram Ti-MOF) is achieved due to the high surface area of Ti-MOF, and the intracellular H O -triggered CO release from the MnCO@Ti-MOF is realized to enable the nanocomplex selectively release CO in tumor cells and kill tumor cells rather than normal cells. Particularly significant is that the real-time fluorescence imaging monitoring of the CO release is realized based on an annihilation effect of the fluorescence after MnCO loading into Ti-MOF and an activation effect of the fluorescence after CO release from Ti-MOF. The quantitative relationship between the fluorescence intensity and the released CO amount is established in great favor of guiding on-demand CO administration. The results demonstrate the advantage of versatile MOFs for high efficient CO delivery and monitoring, which is critical for the improvement of the effectiveness of future therapeutic application.

Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials

“…Taking advantage of high porosity and large specific surface area, porous nanomaterials and macromolecular scaffolds (such as mesoporous silica nanoparticles (MSNs), metal organic frameworks (MOFs), polymeric micelles, and dendrimers) have attracted considerable attention to load a significant amount of CORMs and improve clinical response simultaneously. For example, Carmona et al have successfully encapsulated cationic Mn‐based photoactive ALF472 + and cisplatin (anticancer drug) into the cavities of the anionic matrix of mesoporous silica Al‐MCM‐41 nanoparticles, producing two light‐responsive hybrid CO releasing nanomaterials, named ALF472@Al‐MCM‐41 and ALF472‐cisplatin@Al‐MCM‐41.…”

“…It should be highlighted that the advent of ALF472 + increased anticancer drug loading capacity three‐fold, suggesting the feasible synergistic payload effect and complementary therapeutic property. Furthermore, researchers have demonstrated the advantage of porous MOFs and polymeric micelles for enhanced payload of CORMs, which thus led to increased CO concentration at the disease site and significantly improved the therapeutic effect . Dendrimers are another kind of attractive nanocarrier with highly branched and three‐dimensional structures and have been extensively evaluated as nanocarriers for drug delivery .…”

“…In addition to the controllability of CO release, the real‐time monitoring of CO release is also highly desirable but remains a great challenge . Previous studies have indicated that photoCORMs can be structurally designed as an imageable reporter to visualize the location and extent of CO release .…”

“…Therefore, the innovative integration of nanomaterials with various types of CORMs has emerged as a promising strategy to conquer the aforementioned drawbacks and simultaneously realize the therapeutic application of CO. On the one hand, nanomaterials allow for the loading of hydrophobic CORMs through covalent bond or noncovalent adhesion, thus resolving typical solubility issue and efficiently enhancing the pharmacokinetic properties . Particularly, the use of porous nanomaterials and macromolecular scaffolds can not only enhance the payload of water‐insoluble CORMs, but also efficiently trap the potentially toxic metal fragments, which prevents possible side effects occurring . On the other hand, nanomaterials can be used as targeted CORMs delivery and controllable CO release .…”

“…Copyright 2017, American Chemical Society. b) Reproduced with permission . Copyright 2018, Wiley‐VCH.…”