Tumor microenvironment conversion through intelligent nanomedicine: a paradigm shift in overcoming chemoresistance
6 affiliations
- 1Cancer Research Center, Semnan University of Medical Sciences
- 2Social Determinants of Health Research Center, Semnan University of Medical Sciences
- 3Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences
- 4Department of Physics, University of Zabol
- 5Faculty of Applied Sciences and Biotechnology, Shoolini University
- 6Department of Chemistry, College of Natural Science, Yeungnam University
Abstract
Chemoresistance remains a major challenge in effective cancer management, significantly limiting the therapeutic efficacy of conventional chemotherapy and contributing to tumor recurrence, metastasis, and poor clinical outcomes. Increasing evidence highlights the pivotal role of the tumor microenvironment (TME) in driving therapeutic resistance through complex biological and physicochemical barriers, including hypoxia, acidic pH, abnormal vasculature, elevated interstitial fluid pressure, immune suppression, and dense extracellular matrix deposition. These TME-associated factors collectively impair drug penetration, promote tumor survival, and reduce chemosensitivity. Consequently, contemporary anticancer strategies are shifting from direct tumor cell eradication toward dynamic modulation and conversion of the TME. In this context, intelligent nanomedicine has emerged as a transformative platform capable of precisely responding to endogenous and exogenous stimuli such as pH, redox gradients, hypoxia, enzymes, light, and magnetic fields for site-specific drug delivery and controlled therapeutic activation. Stimuli-responsive nanocarriers not only enhance intratumoral drug accumulation and penetration but also actively remodel the TME through immunomodulation, vascular normalization, extracellular matrix degradation, photodynamic and photothermal effects, and catalytic reactive oxygen species generation. Such multifunctional nanosystems can effectively reverse chemoresistance by reprogramming the tumor milieu into a therapeutically responsive state. This review comprehensively discusses recent advances in intelligent nanomedicine-mediated TME conversion strategies, their mechanistic role in overcoming chemoresistance, and their translational potential in precision oncology. Collectively, TME-targeted intelligent nanomedicine represents a paradigm shift in cancer therapeutics, offering new opportunities for improving therapeutic efficacy while minimizing systemic toxicity.
Related
- Nanomedicine strategies for overcoming the blood–brain barrier in central nervous system drug delivery: mechanisms, advances, and challenges
- Tetrahedral DNA Nanostructures: A Structural-Family-Aware Review from Computational Design and Biological Stability to Translational Nanomedicine
- The EPR effect in human tumors: a critical re-evaluation of a nanomedicine dogma and a call for new targeting paradigms
- Artificial intelligence and machine learning-guided bio-orthogonal engineering of smart soft polymeric nanocarriers for precision drug delivery and translational nanomedicine
- An Integrated Artificial Intelligence Framework for Nanomedicine Engineering
BibTeX
@article{hasannia2026tumor,
title = {{Tumor microenvironment conversion through intelligent nanomedicine: a paradigm shift in overcoming chemoresistance}},
author = {Maliheh Hasannia and Mahdi Abounoori and Fatemeh Mahmoudian and Maryam Shirzad and Abbas Rahdar and Selamu Duguna and Sadanand Pandey},
journal = {Frontiers in Oncology},
year = {2026},
month = jun,
doi = {10.3389/fonc.2026.1812990},
url = {https://doi.org/10.3389/fonc.2026.1812990},
note = {CC BY},
}
RIS
TY - JOUR
TI - Tumor microenvironment conversion through intelligent nanomedicine: a paradigm shift in overcoming chemoresistance
AU - Maliheh Hasannia
AU - Mahdi Abounoori
AU - Fatemeh Mahmoudian
AU - Maryam Shirzad
AU - Abbas Rahdar
AU - Selamu Duguna
AU - Sadanand Pandey
PY - 2026
DA - 2026/06/17
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1812990
UR - https://doi.org/10.3389/fonc.2026.1812990
AB - Chemoresistance remains a major challenge in effective cancer management, significantly limiting the therapeutic efficacy of conventional chemotherapy and contributing to tumor recurrence, metastasis, and poor clinical outcomes. Increasing evidence highlights the pivotal role of the tumor microenvironment (TME) in driving therapeutic resistance through complex biological and physicochemical barriers, including hypoxia, acidic pH, abnormal vasculature, elevated interstitial fluid pressure, immune suppression, and dense extracellular matrix deposition. These TME-associated factors collectively impair drug penetration, promote tumor survival, and reduce chemosensitivity. Consequently, contemporary anticancer strategies are shifting from direct tumor cell eradication toward dynamic modulation and conversion of the TME. In this context, intelligent nanomedicine has emerged as a transformative platform capable of precisely responding to endogenous and exogenous stimuli such as pH, redox gradients, hypoxia, enzymes, light, and magnetic fields for site-specific drug delivery and controlled therapeutic activation. Stimuli-responsive nanocarriers not only enhance intratumoral drug accumulation and penetration but also actively remodel the TME through immunomodulation, vascular normalization, extracellular matrix degradation, photodynamic and photothermal effects, and catalytic reactive oxygen species generation. Such multifunctional nanosystems can effectively reverse chemoresistance by reprogramming the tumor milieu into a therapeutically responsive state. This review comprehensively discusses recent advances in intelligent nanomedicine-mediated TME conversion strategies, their mechanistic role in overcoming chemoresistance, and their translational potential in precision oncology. Collectively, TME-targeted intelligent nanomedicine represents a paradigm shift in cancer therapeutics, offering new opportunities for improving therapeutic efficacy while minimizing systemic toxicity.
SN - 2234-943X
ER -