Precision nanomedicine - navigating the tumor microenvironment for enhanced cancer immunotherapy and targeted drug delivery

Sep 23, 2026

Cancer treatment has been transformed by immunotherapy and nanomedicine, yet tumor microenvironment (TME) complexities drive resistance, off-target effects, and immune suppression. This review synthesizes recent progress in nanoparticle-mediated immunotherapy, biomimetic platforms, and personalized strategies to improve efficacy while reducing systemic toxicity. It covers nanoparticle drug-delivery systems, stimuli-responsive and targeted approaches, TME remodeling, and combination regimens blending physical and immunological tactics. Future directions emphasize optimized nanoformulations, multi-modal treatments, and biomarker-guided personalization to strengthen clinical outcomes.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages37

Reading Time1 h 33 min

AccessFree to download

Introduction

Nanoparticle-based approaches

Combination therapies

Sabit etal. Molecular Cancer (2025) 24:160 [https://doi.org/10.1186/s12943-025-02357-z](https://doi.org/10.1186/s12943-025-02357-z) Molecular Cancer REVIEW Open Access Precision nanomedicine: navigating the tumor microenvironment for enhanced cancer immunotherapy and targeted drug delivery Hussein Sabit1*, Timothy M. Pawlik2*, Faisal Radwan3, Mohamed Abdel-Hakeem4, Shaimaa Abdel-Ghany5, Al-Hassan Soliman Wadan6, Mokhtar Elzawahri1, Ahmed El-Hashash7 and Borros Arneth8 Abstract Cancer treatment has been revolutionized by immunotherapy and nanomedicine, offering innovative strategies to overcome the tumor microenvironment (TME) complexities. However, challenges such as therapeutic resistance, off-target effects, and immune suppression necessitate advanced delivery systems and combination approaches. Recent advancements in nanoparticle-based therapies, biomimetic platforms, and personalized immunotherapy provide promising solutions to enhance therapeutic efficacy while minimizing systemic toxicity. This review explores recent nanoparticle-mediated immunotherapy developments, highlighting strategies to optimize drug delivery, remodel the TME, and improve patient-specific treatment outcomes. A comprehensive review of recent literature focused on nanoparticle-based drug delivery, stimuli-responsive systems, biomimetic nanoplatforms, and personalized immunotherapy approaches. The effectiveness of combination therapies integrating physical and immunological strategies was also analyzed. Nanoparticle-mediated immunotherapy enables precise targeting and controlled drug release, significantly improving therapeutic outcomes. Biomimetic nanoplatforms enhance immune modulation and drug bioavailability, while personalized immunotherapy, guided by predictive biomarkers, tailors treatment to individual patients. Advanced nanomedicine strategies, including TME remodeling, targeted genome editing, and combination immunotherapies, offer promising avenues for overcoming limitations in conventional cancer treatments. Future research should optimize nanoformulations, integrate multi-modal treatment strategies, and refine biomarker-driven personalization to enhance clinical outcomes. Keywords Nanomedicine, Immunotherapy, Cancer therapy, Drug delivery, Tumor microenvironment *Correspondence: Hussein Sabit [hussein.sabit@must.edu.eg](hussein.sabit@must.edu.eg)[ ](hussein.sabit@must.edu.eg)Timothy M. Pawlik [tim.pawlik@osumc.edu](tim.pawlik@osumc.edu) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, 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 you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. 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-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.) Sabit etal. Molecular Cancer (2025) 24:160 Introduction Cancer remains one of the most formidable challenges in modern medicine, with its complexity and heterogeneity posing significant obstacles to effective treatment. Traditional therapies such as chemotherapy, radiation, a

FAQs

What barriers in the tumor microenvironment limit cancer immunotherapy?

Immunosuppressive conditions, hypoxia, and physical barriers such as collagen deposition can reduce immunotherapy efficacy.

How do nanoparticle-based systems improve targeted cancer drug delivery?

Nanocarriers can be engineered to respond to TME-specific stimuli like acidic pH, hypoxia, or overexpressed enzymes, enabling controlled release at the tumor site.

Why are combination therapies emphasized in the review?

Combining immunotherapy with chemotherapy, photothermal therapy, or targeted delivery can simultaneously target multiple pathways behind tumor growth and therapeutic resistance.

Sep 23, 2026

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