Mapping nanodelivery design for liver fibrosis: A mechanism-informed framework for functional integration

Liver fibrosis is sustained by interdependent hepatic stellate cell activation, inflammatory amplification, and gene-regulatory remodeling, yet nanodelivery platforms are commonly discussed by carrier class rather than by the functions required to address these disease mechanisms. This review develops a mechanism-function framework linking these pathological axes to six delivery functions: targeted delivery, drug stability, controlled release, bioavailability, biocompatibility, and immune evasion. After structured screening, formulation-level deduplication, supporting-information review, and independent verification, 124 eligible studies yielded 129 analytical units spanning HSC inactivation (n = 50), anti-inflammation (n = 33), and gene modulation (n = 46). Each unit was coded as directly demonstrated, assessed but not demonstrated, or not assessed/insufficiently reported for each function. The analysis identified modality-dependent integration patterns rather than a universal hierarchy. HSC-directed systems combined biocompatibility and targeted delivery with greater controlled-release integration; anti-inflammatory systems showed co-leading biocompatibility and targeted delivery, with TD-BC showing the highest raw co-occurrence and CR-BC the highest Jaccard similarity; and gene-modulation systems showed co-leading targeted delivery and biocompatibility reinforced by bioavailability. Direct evidence for drug stability and immune evasion remained comparatively sparse. All 30 core modality-level sensitivity comparisons preserved the top-two function sets and leading Jaccard pairs. BMS-986263 illustrates partial completion of the translational evidence chain: active-payload exposure and clinical tolerability were demonstrated, whereas cell-selective delivery, cargo integrity, release behavior, and immune-evasion performance were not directly established. These findings support an evidence-guided shift from maximal structural complexity toward mechanism-aligned, manufacturable platforms evaluated through active-payload exposure, target-compartment delivery, repeat-dose safety, and disease-stage-appropriate clinical design.