Metal-Organic Frameworks (MOFs) for Targeted Drug Delivery: A Review of Design-to-Release Correlations.

Abstract

BACKGROUND: Metal-organic frameworks (MOFs) are crystalline porous materials that consist of adjustable metal nodes and organic linkers. These properties enable MOFs to act as effective vehicles for drug delivery when designed to control the breakdown or opening of the framework upon receiving a trigger, such as a biological or chemical stimulus [1, 2, 3, 4]. Even though the latest advances in research into MOFs have expanded the literature, the published information on the correlation of the factors concerning the design of MOFs (the type of metal node and linker used, the size of the particles, and surface treatment) with the process of the release of drugs has not been conducted to the fullest extent. OBJECTIVE: This study aims to conduct a systematic review of the (i) synthesis and physico-chemical characterization methods applied to the development of stimuli-responsive MOFs used for targeted drug delivery and of the (ii) design-to-release relationships that govern the use of pH, redox, light, temperature, and enzymatic triggers. METHODS: The review follows PRISMA 2020 [5]. PubMed, Scopus, Web of Science, and ScienceDirect were searched for English-language primary research published during 2014-2025. Two reviewers screened records and extracted information on MOF identity, synthesis, characterisation, loading, release and biological outcomes. Complete screening, extraction and appraisal records are unavailable for independent verification. The present synthesis is qualitative; selected numerical observations are attributed to individual studies, without pooled estimates or cross-study regression. pH-, redox-, light-, temperature- and enzyme-responsive systems illustrate the diversity of MOF-based delivery. ZIF-8, MIL-family, UiO-66 and porphyrinic carriers offer different loading and release strategies. Loading capacity, particle size and surface modification influence performance, but comparisons depend on cargo, formulation and assay conditions. The available documentation does not support a pooled release ratio, a BET-loading regression, or a universal size optimum. Animal studies were appraised with SYRCLE [6].

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