Nanocarrier-mediated targeting of NF-κB and JAK/STAT signaling pathways in hepatocellular carcinoma - mechanisms and therapeutic strategies

Sep 22, 2026

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Hepatocellular carcinoma (HCC) remains a major global cause of cancer-related deaths, driven in part by aberrant activation of NF-κB and JAK/STAT signaling. This review critically analyzes recent advances in nanocarrier-mediated targeting of these pathways in HCC, detailing pathway crosstalk and consequences for inflammation, angiogenesis, hepatocarcinogenesis, and resistance to immunotherapy and chemotherapy. It summarizes diverse nanoplatforms for improved delivery of inhibitors, nucleic acids, and combination regimens, emphasizing ligand-functionalized and stimulus-responsive systems for targeted liver therapy. It also discusses ligand-independent control, plus scalability, biosafety, and regulatory considerations.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Introduction

NF-κB and JAK/STAT signaling in HCC

Nanocarrier-mediated therapeutic strategies

Azhar etal. Journal of Experimental & Clinical Cancer Research (2026) 45:140 [https://doi.org/10.1186/s13046-026-03715-5](https://doi.org/10.1186/s13046-026-03715-5) Journal of Experimental & Clinical Cancer Research REVIEW Open Access Nanocarrier-mediated targeting of NF-κB and JAK/STAT signaling pathways in hepatocellular carcinoma: mechanismsand therapeutic strategies Muhammad Azhar1†, Yang Duan1†, Muhammad Ahmad2† and Haichuan Wang1* Abstract Hepatocellular carcinoma (HCC) remains a major global cause of cancer-related deaths. HCC development, immune evasion, and treatment resistance are significantly influenced by the aberrant activation of the NF-κB and JAK/STAT signaling pathways. The review provides a thorough and critical analysis of recent developments in nanocarriermediated targeting of NF-κB and JAK/STAT pathways in HCC. It demonstrates the molecular interactions between various pathways and their implications for inflammation, angiogenesis, hepatocarcinogenesis, and resistance to both immunotherapy and chemotherapy. A variety of nanoplatforms, such as polymeric nanoparticles, lipidbased systems, inorganic nanomaterials, and biomimetic carriers, are designed to enhance the delivery of smallmolecule inhibitors, nucleic acids, and combination therapies, improving pharmacokinetic and pharmacodynamic profiles. The review highlights ligand-functionalized and stimulus-responsive nanocarriers designed for controlled drug release and targeted therapy in the liver environment. Co-modulation of NF-κB and JAK/STAT signaling via nanotechnology enhances antitumor efficacy and decreases systemic toxicity, as supported by preclinical and recent translational data. Lastly, important issues such as scalability, biosafety, and regulatory concerns are discussed. Future directions for integrating precision cancer techniques with nanomedicine are proposed. This analysis emphasizes the therapeutic potential of targeting the NF-κB and JAK/STAT pathways with nanotechnology to enhance outcomes in HCC. Keywords Hepatocellular carcinoma, NF-κB signaling, JAK/STAT pathway, Nanotechnology-based drug delivery, Targeted cancer therapy †Muhammad Azhar, Yang Duan and Muhammad Ahmad contributed equally as first co-author. *Correspondence: Haichuan Wang [haichuan.wang@wchscu.edu.cn](haichuan.wang@wchscu.edu.cn) Full list of author information is available at the end of the article © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The)[. The](http://creativecommons.org/licenses/by/4.0/. The)[ ](http://creativecommons.org/licenses/by/4.0/. The)Creative Commons Public Domain Dedication waiver ([http://creativecommons.org/publicdomain/zero/1.0/](http://creativecommons.org/publicdomain/zero/1.0/)) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Azhar et al. Journal of Experimental & Clinical Cancer Research (2026) 45:140 Page 2 of 19 Graphical Abstract Introduction Hepatocellular carcinoma (HCC) was responsible for 830,180 deaths globally in 2020, making it the most prevalent primary liver cancer [1]. Additionally

FAQs

Why are NF-κB and JAK/STAT signaling important in hepatocellular carcinoma (HCC)?

The review states that HCC development, immune evasion, and treatment resistance are significantly influenced by aberrant activation of NF-κB and JAK/STAT signaling pathways.

What does the review cover about nanocarrier-mediated targeting?

It provides a thorough analysis of recent developments, including molecular interactions between pathways and how nanocarriers are designed to enhance delivery and targeted therapy in the liver environment.

How do nanotechnology-based co-modulation strategies affect treatment outcomes in HCC?

Co-modulation of NF-κB and JAK/STAT signaling via nanotechnology is described as enhancing antitumor efficacy while decreasing systemic toxicity, supported by preclinical and translational data.

Sep 22, 2026

Upload by Jasmine