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Nevertheless, their clinical translation is limited by inefficient intracellular delivery due to poor membrane permeability, endo\/lysosomal entrapment, and instability in complex biological environments. Metal\u2010organic frameworks (MOFs), featuring high porosity, tunable structures, mild encapsulation conditions, versatile surface modification, and stimulus\u2010responsive degradation, have emerged as attractive material platforms for biomacromolecule protection and intracellular delivery. This review summarizes the design evolution of biomacromolecule\u2013MOF composites from empirical construction to rational design and AI\u2010assisted screening. Recent advances in AI\u2010assisted enzyme\u2013MOF and drug\u2010delivery MOF design are further discussed as emerging tools for synergistic integration of multiple functions. 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