At the cutting edge of cancer treatment, scientists at the Fralin Biomedical Research Institute at Virginia Tech Carilion (VTC) alongside their global collaborators are harnessing the immense potential of nanotechnology to revolutionize immuno-oncology. In a pair of groundbreaking review articles recently published in premier journals, these researchers dissect the emerging nexus of nanomedicine and immune engineering, shedding light on innovative approaches aimed at overcoming the formidable defenses that tumors deploy against the body’s natural immune responses. This burgeoning field offers promising new avenues for precise, effective cancer therapies, especially targeting stubborn solid tumors that have historically resisted conventional immunotherapies.
Traditional immunotherapies rely on activating the body’s immune system to recognize and eradicate cancer cells but frequently face obstacles imposed by the tumor microenvironment. Tumors evolve sophisticated mechanisms to evade immune detection, including suppressing immune cell activity or creating physical barriers that prevent immune infiltration. This inhibitory milieu complicates therapeutic success, necessitating novel delivery systems and immune modulation strategies to tip the scales back in favor of the host’s defenses. Nanotechnology introduces unprecedented control at the molecular and cellular levels, allowing therapeutic agents to be engineered with properties tailored to penetrate tumors, modulate immune responses, and synergize with existing treatment modalities.
DaeYong Lee, an assistant professor at the Fralin Biomedical Research Institute and a key figure spearheading this initiative, articulates the crux of the challenge: “Our immune system wields a remarkable capacity to target cancer cells, but tumors suppress or evade these defenses through complex mechanisms. By integrating nanoengineering with immunology, we are pioneering therapeutic designs that enhance specificity and efficacy.” The reviews consolidate insights from diverse laboratories and disciplines, providing a comprehensive framework that maps current achievements and technological potentials within nanomedicine-infused cancer immunotherapy.
The first review, featured in Nature Cancer, co-authored by Lee alongside Wen Jiang and Betty Y.S. Kim from the University of Texas MD Anderson Cancer Center, elucidates the multifaceted applications of nanotechnology in oncology. Primarily, it focuses on enhancing drug delivery systems to improve biodistribution and target specificity. Nanocarriers can navigate the tumor microenvironment more effectively than conventional delivery methods, offering controlled release, reduced systemic toxicity, and enhanced accumulation within tumor tissue through the enhanced permeability and retention (EPR) effect. This precision targeting not only spares healthy cells but also maximizes therapeutic payload efficacy directly at the disease site.
Moreover, the review highlights strategies where nanotechnology actively reprograms the tumor microenvironment to convert immunosuppressive conditions into immune-permissive ones. Nanoparticles can be engineered to deliver immunomodulators that shift macrophage phenotypes from tumor-promoting (M2) to tumor-fighting (M1), increase cytotoxic T lymphocyte infiltration, and inhibit regulatory T cells that blunt immune responses. Some nanoformulations are designed to synergize with emerging immunoengineering approaches, such as mRNA vaccine platforms and genetically engineered cellular therapies like CAR-T cells, amplifying their impact in solid tumor contexts where efficacy has been traditionally limited.
Concurrently, a complementary review published in Trends in Cancer delves into the crucial immune process of phagocytosis—the mechanism by which macrophages engulf and dispose of cancer cells. Co-authored by Lee in collaboration with researchers from the Korea Advanced Institute of Science and Technology, this article explores how nanomedicine can restore or augment this innate immune function, which tumors often impair to survive. One salient mechanism tumors exploit is the expression of “don’t eat me” signals, such as CD47, that send inhibitory cues to macrophages, preventing phagocytosis.
Nanotechnological innovations target these evasion strategies by designing particles capable of blocking these inhibitory signals, thereby unmasking cancer cells to the immune system. Another frontier discussed involves engineering macrophages with chimeric antigen receptors (CARMs), endowing these immune cells with enhanced specificity toward tumor antigens and reinforcing their phagocytic activity against solid malignancies. Additionally, certain nanomedicine platforms bolster “eat me” signals on tumor cells, molecular flags that alert macrophages to initiate clearance, thus restoring the immune system’s surveillance and elimination functions.
Together, these integrated studies chart a path toward next-generation immunotherapies that harness the intersection of molecular nanotechnology, cellular engineering, and immunology. The ability to deliver payloads at nanoscale precision, modulate immune cell phenotypes, and reprogram the tumor microenvironment marks a significant leap beyond traditional approaches, paving the way for more effective interventions against cancers that have hitherto evaded therapeutic control.
However, translating these technological advances from bench to bedside remains formidable. Lee emphasizes the ongoing challenge: “The objective is to convert these scientific discoveries into therapies that are not only safe and effective but also accessible to patients worldwide.” Clinical translation involves navigating regulatory hurdles, manufacturing scalability, and ensuring that nanoengineered therapies exhibit robust efficacy with minimal adverse effects in diverse patient populations.
Funding from institutions such as the National Institutes of Health, American Cancer Society, and the Radiological Society of North America, among others, underscores the critical support underpinning this research. These partnerships enable multidisciplinary collaborations that accelerate developments in nano-immunoengineering, bringing closer the prospect of versatile, personalized cancer immunotherapies.
The fusion of nanotechnology and immunology represents a transformative frontier in oncology. By tailoring immune responses with nano-scale interventions, researchers aspire to outmaneuver tumor defenses with therapies capable of durable remissions, reduced side effects, and broader applicability across cancer types. This paradigm shift is set to redefine cancer treatment landscapes and embolden the immune system’s role as a powerful frontline against malignancy.
As the field advances, continued exploration of nanoparticle design, cellular reprogramming, and immune checkpoint modulation is anticipated to yield innovative therapeutic platforms. Interdisciplinary research will be pivotal in uncovering optimal combinations of nanoformulations and immunotherapies, ultimately contributing to a new era of precision oncology where treatments are custom-fit to the molecular and cellular tumor context.
The journey toward fully realizing the promise of nanomedicine-enhanced immunotherapy is underway, with foundational scientific insights establishing a robust framework for future breakthroughs. The possibilities unlocked through such technologies herald a significant leap forward in cancer patient care, fostering hope for more effective and lasting treatments in the quest to eradicate malignancies.
Subject of Research: Cells
Article Title: Nanotechnology for immuno-oncology
News Publication Date: 7-Aug-2025
Web References:
- https://www.nature.com/articles/s43018-025-01025-x
- https://www.cell.com/trends/cancer/abstract/S2405-8033(25)00202-X
Image Credits: Clayton Metz/Virginia Tech
Keywords: Cancer, Nanotechnology, Immunotherapy, Molecular biology
