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Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology has been extensively applied in cancer theranostics due to its high specificity, multiplexing capacity, and programmable genome-editing capability. However, its broad clinical translation remains significantly hindered by substantial physiological barriers─including rapid clearance by the mononuclear phagocyte system and limited tumor penetration imposed by the dense extracellular matrix─as well as suboptimal intracellular delivery, inefficient endosomal escape, and persistent off-target risks. To address these challenges, nanomaterial-based delivery systems offer a versatile and tunable strategy. In this review, we categorize the design of such delivery platforms according to core molecular engineering principles, with a focused discussion on three main material design approaches: noncovalent assembly (using electrostatic and supramolecular host–guest interactions), coordination-driven assembly (employing metal–organic frameworks and metal–ion coordination), and covalent assembly (via stimuli-responsive cross-linking). By examining these distinct molecular assembly strategies, we illustrate how precise structural optimization governs the delivery efficiency and biological performance of CRISPR systems. We further highlight the innovative applications of engineered nanomaterials in cancer diagnostics, including highly sensitive in vitro biomarker detection and dynamic in vivo imaging of tumor progression. Their therapeutic potential is also systematically reviewed, particularly in targeted gene disruption, tumor microenvironment remodeling, and metabolic reprogramming. Finally, we discuss current advances, biosafety issues, and key translational challenges─such as scalable manufacturing and batch-to-batch consistency─facing CRISPR-based nanomedicines. This review aims to provide structurally informed insights that may help overcome existing delivery limitations and guide the future development of precision oncology tools.
Li et al. (Tue,) studied this question.