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Metal-organic frameworks (MOFs) are a fascinating class of crystalline porous materials composed of metal ions and organic ligands. Due to their attractive properties, MOFs can potentially offer biomedical field applications, such as drug delivery and imaging. This study aimed to systematically identify the affecting factors on the MOF characteristics and their effects on structural and biological characteristics. An electronic search was performed in four databases containing PubMed, Scopus, Web of Science, and Embase, using the relevant keywords. After analyzing the studies, 20 eligible studies were included in this review. As a result, various factors such as additives and organic ligand can influence the size and structure of MOFs. Additives are materials that can compete with ligand and may affect the nucleation and growth processes and, consequently, particle size. The nature and structure of ligand are influential in determining the size and structure of MOF. Moreover, synthesis parameters like the reaction time and initial reagents ratio are critical factors that should be optimized to regulate the size and structure. Of note is that the nature of the ligand and using a suitable additive can control the porosity of MOF. The more extended ligands aid in forming large pores. The choice of metallic nodes and organic ligand, and the MOF concentration are important factors since they can determine toxicity and biocompatibility of the final structure. The physicochemical properties of MOFs, such as hydrophobicity, affect the toxicity of nanoparticles. An increase in hydrophobicity causes increased toxicity of MOF. The biodegradability of MOF, as another property, depends on the organic ligand and metal ion and environmental conditions like pH. Photocleavable ligands can be served for controlled degradation of MOFs. Generally, by optimizing these affecting factors, MOFs with desirable properties will be obtained for biomedical applications.

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