CRISPR-Cas-enabled nanocarriers in hepatocellular carcinoma: Emerging gene-editing strategies for precision liver therapy

Hepatocellular carcinoma (HCC) remains a highly deadly global malignancy with limited curative treatments, frequent recurrence, and delayed diagnosis. Gene editing systems using CRISPR-Cas offer great potential to correct cancer-causing mutations, reprogram the tumor microenvironment, and overcome drug resistance mechanisms. Safe, efficient, and targeted delivery systems are critically needed for clinical translation of CRISPR-based therapeutics. Recent advances in nanocarrier technologies including lipid nanoparticles, polymeric systems, and stimuli-responsive platforms have enabled precise delivery of CRISPR cargo to hepatic tissues with improved gene-editing efficiency and biocompatibility. This review summarizes preclinical advances from 2015-2025 in CRISPR-Cas delivery using nanocarriers for HCC therapy, explores gene targets such as TERT, CTNNB1, and TP53, and discusses challenges related to off-target effects, immune responses, and scalability. We emphasize emerging strategies that integrate imaging with responsive biomaterials and AI-driven optimization to improve specificity and therapeutic outcomes. Overall, the integration of CRISPR-Cas systems with advanced nanocarriers marks a paradigm shift in HCC treatment, holding promise for highly personalized and durable gene-based therapies.