Plain-language summary
Non-alcoholic fatty liver disease and cardiovascular disease often appear together, yet most therapies target a single organ at a time. This review reframes the two conditions as one interconnected metabolic problem and builds a design framework that links their shared biology to materials engineering. The authors identify three pathological axes: lipid overload with impaired reverse cholesterol transport; chronic inflammation and oxidative stress driven by Kupffer cell NLRP3 signalling and mitochondrial reactive oxygen species; and gut-liver-vascular dysregulation involving bile acid FXR/TGR5 pathways and microbiota-derived metabolites. Against each axis they map engineering solutions: liver- and heart-targeting ligands such as GalNAc and VCAM-1 binders; HDL-mimetic and exosome-based platforms that restore cholesterol efflux; ROS-, pH-, and enzyme-responsive carriers that release cargo only in the diseased microenvironment; mitochondria-addressed nanostructures including antioxidant nanozymes; and macrophage-reprogramming cytokine mRNA and miRNA payloads. The review closes with translational criteria - biodistribution fidelity, barrier crossing, multi-pathway control, and safety by design - and proposes closed-loop systems that combine AI-guided design with synthetic biology circuits.
Key findings
- NAFLD and cardiovascular disease co-occur through inter-organ metabolic crosstalk that current single-target therapies do not address.
- The review maps three shared pathological axes - lipid overflow, inflammation-oxidative stress amplification, and gut-liver-vascular dysregulation - to matching materials-based interventions.
- Highlighted platforms include organ-targeting ligands, HDL-mimetic and exosome carriers, stimulus-responsive nanoparticles, mitochondrial nanozymes, and macrophage-reprogramming nucleic acid payloads.
- The authors propose actionable translational criteria and closed-loop systems that combine AI-guided design with synthetic biology circuits.
Original abstract
Non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) frequently co-occur, driven by inter-organ metabolic crosstalk that current single-target therapies fail to disrupt. This review reframes NAFLD-CVD comorbidity through a materials-first lens and advances a translational design framework that couples pathophysiology with engineering principles. We synthesize three major pathological axes, including lipid overflow and impaired reverse cholesterol transport, inflammation-oxidative stress amplification driven by Kupffer cell-NLRP3 and mitochondrial ROS/MAPK signaling, as well as gut-liver-vascular dysregulation involving bile acid FXR/TGR5 pathways and microbiota-derived metabolites, and further map these mechanisms to organ-selective and stimulus-responsive therapeutic interventions. Specifically, we highlight liver-heart co-targeting via GalNAc/ASGPR and VCAM-1 ligands, HDL-mimetic and exosome platforms that restore cholesterol efflux, ROS/pH/enzyme-responsive carriers that achieve microenvironment-triggered release and mitochondria-addressed nanodevices including antioxidant nanozymes, Mito-therapeutics, and optogenetically guided CRISPR/RNA payloads that recalibrate energy/redox homeostasis. We further outline macrophage-reprogramming strategies using cytokine mRNA and miRNA modulators to resolve chronic inflammation, and propose closed-loop systems that integrate AI-guided design with synthetic biology circuits for adaptive, multi-organ control. Across platforms, we distill actionable criteria covering clinical translation, biodistribution fidelity, barrier traversal, compensation-proof multi-pathway control, and safety-by-design. This materials-anchored roadmap moves the field from single-organ symptom control to systemic metabolic reprogramming, positioning advanced materials as catalysts for durable, precision therapy in NAFLD-CVD comorbidity.
Frequently asked questions
What did this study find?
Non-alcoholic fatty liver disease and cardiovascular disease often appear together, yet most therapies target a single organ at a time. This review reframes the two conditions as one interconnected metabolic problem and builds a design framework that links their shared biology to materials engineering. The authors identify three pathological axes: lipid overload with impaired reverse cholesterol transport; chronic inflammation and oxidative stress driven by Kupffer cell NLRP3 signalling and mitochondrial reactive oxygen species; and gut-liver-vascular dysregulation involving bile acid FXR/TGR5 pathways and microbiota-derived metabolites. Against each axis they map engineering solutions: liver- and heart-targeting ligands such as GalNAc and VCAM-1 binders; HDL-mimetic and exosome-based platforms that restore cholesterol efflux; ROS-, pH-, and enzyme-responsive carriers that release cargo only in the diseased microenvironment; mitochondria-addressed nanostructures including antioxidant nanozymes; and macrophage-reprogramming cytokine mRNA and miRNA payloads. The review closes with translational criteria - biodistribution fidelity, barrier crossing, multi-pathway control, and safety by design - and proposes closed-loop systems that combine AI-guided design with synthetic biology circuits.
Was this tested in humans or in the laboratory?
This is a review: it summarises and weighs up previously published studies rather than presenting new experiments.
Where can I read the original paper?
The full text lives with the publisher: https://doi.org/10.1016/j.biomaterials.2026.124209
How to cite this paper
Na Jianrong, Huang Lei, Wang Lijuan, Ni Yue, Chen Yisheng, Luo Qiancheng et al.. Advanced materials for non-alcoholic fatty liver disease and cardiovascular disease comorbidity therapeutics.. Biomaterials. 2026, 2026-04-19. DOI: 10.1016/j.biomaterials.2026.124209
Source & verification
- Journal: Biomaterials
- Published: 19 April 2026
- DOI: 10.1016/j.biomaterials.2026.124209
- PubMed ID: 42001540
- Indexed via: pubmed
- MeSH terms: Humans, Non-alcoholic Fatty Liver Disease, Animals, Cardiovascular Diseases, Biocompatible Materials