Nanotechnology-based drug delivery systems may enhance sorafenib's therapeutic efficacy in (HCC).
Sorafenib is limited by poor pharmacokinetics, dose-limiting toxicities, and resistance.
Innovations in drug delivery include lipid-based, polymeric, inorganic, and biogenic .
Active tumor targeting strategies, such as receptor-mediated approaches, may improve drug localization.
Stimuli-responsive systems can achieve localized drug release based on tumor microenvironment cues.
Co-delivery with other agents could amplify antitumor activity and help overcome resistance.
Preclinical evidence shows improved pharmacokinetics and tumor accumulation, but challenges in production and safety remain.
Simplified
(HCC) remains a leading cause of cancer-related mortality worldwide, with systemic therapies offering only limited benefit. Sorafenib, the first-line multi-kinase inhibitor, is constrained by poor pharmacokinetics, dose-limiting toxicities, and the rapid emergence of resistance. Nanotechnology-based drug delivery systems (NDDS) provide promising strategies to address these limitations. This review summarizes recent NDDS innovations that enhance sorafenib's therapeutic efficacy in HCC. Major classes, including lipid-based, polymeric, inorganic, and biogenic platforms, are discussed together with modifications for passive or active tumor targeting, such as asialoglycoprotein receptor-mediated approaches. Special attention is given to stimuli-responsive systems that exploit tumor microenvironmental cues to achieve localized drug release. Co-delivery strategies that combine sorafenib with chemotherapeutics, RNA interference agents, or immune modulators are also highlighted for their capacity to amplify antitumor activity and overcome resistance. Artificial intelligence (AI) is emerging as a tool to support the rational design and personalization of nanomedicines. While encouraging preclinical evidence demonstrates improved pharmacokinetics, tumor accumulation, and efficacy, challenges in scalable production, biosafety, and regulatory approval remain. Collectively, these developments emphasize the potential of sorafenib nanomedicines while underscoring the need to resolve key barriers for clinical translation.
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Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors have reviewed the manuscript and provided their consent for publication. Competing interests: The authors declare no competing interests.
