Biomedical Metal-Organic Framework Materials: Perspectives and Challenges

Abstract

Metal-organic framework (MOF) materials are gaining significant interest in biomedical research, owing to their high porosity, crystallinity, and structural and compositional diversity. Their versatile hybrid organic/inorganic chemistry endows MOFs with the capacity to retain organic (drug) molecules, metals, and gases, to effectively channel electrons and photons, to survive harsh physiological conditions such as low pH, and even to protect sensitive biomolecules. Extensive preclinical research has been carried out with MOFs to treat several pathologies and, recently, their integration with other biomedical materials such as stents and implants has demonstrated promising performance in regenerative medicine. However, there remains a significant gap between MOF preclinical research and translation into clinically and societally relevant medicinal products. Here, we outline the intrinsic features of MOFs and discuss how these are suited to specific biomedical applications like detoxification, drug and gas delivery, or as (combination) therapy platforms. We furthermore describe relevant examples of how MOFs have been engineered and evaluated in different medical indications, including cancer, microbial, and inflammatory diseases. Finally, we critically examine the challenges facing their translation into the clinic, with the goal of establishing promising research directions and more realistic approaches that can bridge the translational gap of MOFs and MOF-containing (nano)materials.

Keywords: biomedicine; metal-organic frameworks; metallotherapy; nanoparticles; porous materials.

Graphical abstract

Translational challenges and perspectives of metal-organic framework materials in biomedicine: the state-of-the-art in the medicinal application is reviewed and potential barriers and avenues to clinical translation are explored.

Figure 1. Publication record for metal-organic frameworks in biomedicine.

(a) Proportion of all metal-organic framework (MOF) publications for biomedical applications as compared to all other applications (left), and their growth (right). (b) The most prominent MOF families explored in biomedical research. (c) Most common metals used in MOF biomedical research (this includes metal nodes in the framework, metals doped into the framework and metals which are part of other materials that have been explored in combination with MOFs). (d) Distribution of MOF papers by therapeutic indication, showing the total number of publications per indication as well as the growth of each major application since 2010. (e) Publication numbers of MOFs for drug delivery, showing the significant proportion of MOFs used as drug carriers. (f) Proportion (left) and growth (right) of MOF research in anticancer drug delivery since 2015, as compared to other carrier (nano)materials. Data, comprising the period 2010-2022 (except for panel f, which comprises 2015-2022), was obtained by systematic search of the SCOPUS database of journal publication^[22] (NB: details of search terms are also provided in the corresponding reference 22).

Figure 2. Metal-organic framework properties for biomedical applications.

The high porosity, surface area and metal-organic composition endows metal-organic frameworks (MOFs) with potential use as detoxifying agents, drug and gas carriers, and as active therapeutic platforms. (a) The adsorptive capacity of the framework can be exploited to capture harmful substances such as radioisotopes and excess drugs, facilitating removal from the body. (b) The high porosity and structural versatility of MOFs allow them to load a wide variety of drug cargoes, from low molecular weight compounds to biomacromolecules. (c) Gases are a therapeutic cargo that MOFs have demonstrated a unique ability to load and deliver with high efficiency. They can be catalytically generated by the MOF or directly loaded into the structure. (d) Both the metal and the organic linker of the framework can act as active therapeutic entities, often in response to endogenous (e.g., pH and enzyme) or exogenous stimuli (e.g., light, radiation and ultrasound), and potentially in combination with other treatment strategies.

Figure 3. Metal-organic framework formulation, administration, and therapeutic applications.

(a) Metal-organic framework (MOF) formulation and post-synthetic strategies used to enable and enhance preclinical and clinical application of MOFs. (b) Main routes of administration of MOF formulations, the major formulation requirements for each form of administration, and examples of MOFs that have been shown to be compatible with each route. (c) Four of the most common therapeutic applications of MOFs showing different treatment approaches and how the intrinsic functionalities of MOFs are applied for that indication. Microscopy images for gel/emulsion and surface-embedding (panel 3a) were reproduced with permission (Copyright 2019, Royal Society of Chemistry;^[211] and Copyright 2021, Elsevier^[212]).

Figure 4. Challenges in metal-organic framework pharmaceutical development and clinical translation.

The perspective on metal-organic framework (MOFs) in biomedicine and the translational challenges that remain. MOFs hold promise in niche areas where their properties have the potential to allow them to outperform current therapeutic materials; most notably for gas delivery, detoxification purposes and as active (immuno)therapeutic entities. However, MOF-based materials face considerable difficulty in attracting interest from stakeholders outside of academia, such as clinicians and the pharmaceutical industry. This is, in part, due to strong competition with currently used biomedical materials, but also due to the lack of rigorous preclinical data, challenging manufacturing protocols, and non-standardized characterization and quality control. Addressing these challenges is expected to help drive MOFs across the bench-to-bedside gap in the right indications.