Conventional cancer therapies risk causing damage to healthy tissue while working to destroy cancer cells. Researchers are developing novel therapeutics based on nanotechnology to overcome this limitation, as well as to improve the pharmacokinetics of a pharmaceutical and reduce the related toxicities (Nat Rev Drug Discov 2021; https://doi.org/10.1038/s41573-020-0090-8).
Another encouraging area of nanotechnology in oncology is its use in enhancing immunotherapy (Nanoscale 2019; doi: 10.1039/c9nr05371a). T cells are important fighters in an immune response, and T cell-based immunotherapy of cancer is a rapidly developing field. While immunotherapy has already been established as an exciting and potentially highly effective treatment option for various types of cancer, one important challenge remains—stimulate antitumor immunity of primary T cells in vivo.
To tackle this issue, scientists at Ohio State University developed nanotechnology to boost activation of T cells at the cancer tumor site in a way that improved their interactions with an antibody therapy undergoing clinical trial testing. The study, which was conducted in mouse models of cancer, was published in the journal Nature Communications (2021; https://doi.org/10.1038/s41467-021-27434-x).
The research was led by the Dong lab, which has long focused on nanoparticle delivery of messenger RNA (mRNA) as a therapeutic strategy. In the current study, the team hypothesized that delivery of costimulatory receptor mRNA to tumor-infiltrating T cells would enhance the antitumor effects of antibodies while lowering the chances for whole-body side effects.
To explore nanoparticles for delivering mRNA into T cells, the investigators designed and synthesized a library of phospholipid and glycolipid derivatives (PLs and GLs) and used these materials to devise biomimetic nanoparticles for mRNA delivery. The team chose to utilize the phospholipid-derived nanoparticle, PL1, to deliver the costimulatory receptor mRNA.
Next, the researchers loaded the nanoparticle cargo: (mRNA) carrying instructions to produce molecules that T cells express as part of their immune system function. The researchers injected these nanoparticles directly into the tumor site in mouse models of specific cancers, which entered tumor-infiltrating T cells to generate and amplify specific receptors on their surfaces enabling additional functions, including proliferation, recruitment of other immune cells, and production of helpful proteins.
The team waited 6 hours until the cells produced enough receptors and then injected antibodies into the tumors. The combination of PL1-OX40 mRNA and anti-OX40 antibody demonstrated significantly improved antitumor activity compared to anti-OX40 antibody alone in multiple tumor models. Tests of the combined treatment regimen produced the best results in mouse models of melanoma and B-cell lymphoma. Experimental monoclonal antibodies delivered 6 hours later could then bind to those receptors on T cells which triggered their cancer cell-killing functions. The nanoparticle and antibody delivery eliminated tumors in 60 percent of the mice—a significantly better outcome than treatment with the antibody alone. Moreover, the immune response enhancement had a lasting effect: lymphoma cells injected later into the treated tumor-free mice were unable to survive long enough to form tumors.
The new nanotechnology was effective in melanoma as well. When the team supplemented the combination treatment with the two additional antibodies that disrupt cancer cells’ ability to block the immune response, the approach resulted in a 50 percent complete response in the mice and protection against a later tumor rechallenge.
Oncology Times reached out to senior author, Yizhou Dong, PhD, for additional insights into their study. Dong is Associate Professor in the Division of Pharmaceutics and Pharmacology of the College of Pharmacy at The Ohio State University. His research focuses on the design and development of biotechnology platforms for the treatment of genetic disorders, infectious diseases, and cancers.
Oncology Times: A great number of nanoformulations have been reported as drug delivery systems to be applied in cancer treatment. What was the rationale for the design of this system?
Dong: “Phospholipids and glycolipids are natural components of the cell membrane. Taking advantage of this unique characteristic of these two types of lipids, we designed a library of phospholipid and glycolipid biomimetic materials (PL and GL lipids) to improve mRNA delivery. These PL and GL lipids are composed of a biomimetic head (phosphate head or glyco head), an ionizable amino core, and multiple hydrophobic tails. Their ionizable property makes them neutral at physiological pH and becomes positively charged at low pH.”
Oncology Times: What were some of the factors which posed challenges in the development of the nanoparticle delivery system of messenger RNA? What strategies were employed to surmount these challenges?
Dong: “Effective and safe delivery of mRNA remains the key challenge for clinical translation of nanoparticle formulations. We mimic nature using chemical structures such as phospholipid, glycolipid, and many other molecules from mammalian cells. By systematic exploration and optimization of the formulations, we can match delivery systems with therapeutic indications.”
Oncology Times: What are the potential clinical implications of the findings of this study?
Dong: “In this work, we developed a phospholipid-derived nanoparticle to deliver OX40 or CD137 mRNA to T cells in the tumor microenvironment, which enhances the efficacy of agonistic antibody therapy in preclinical tumor models. This treatment strategy is compatible with multiple administration routes and works in synergy with checkpoint inhibitors, demonstrating the broad applicability of this treatment regimen under diverse therapeutic situations. Additionally, the results lay a solid foundation for the exploration of more effective combinations using costimulatory receptors and agonistic antibodies for cancer immunotherapy.”
Oncology Times: Nanotechnology targets cancer cells more exactly to spare healthy tissues. Are there any possible side effects of nanotechnology for cancer?
Dong: “Many strategies have been investigated to improve the targeting efficiency of cancer cells. Different from direct targeting cancer cells, we aim to modulate T cells in the tumor microenvironment using nanoparticles delivering mRNA encoding costimulatory receptors in combination with the corresponding agonistic antibody as a strategy to enhance cancer immunotherapy.”
News
Scientists Begin $14.2 Million Project To Decode the Body’s “Hidden Sixth Sense”
An NIH-supported initiative seeks to unravel how the nervous system tracks and regulates the body’s internal organs. How does your brain recognize when it’s time to take a breath, when your blood pressure has [...]
Scientists Discover a New Form of Ice That Shouldn’t Exist
Researchers at the European XFEL and DESY are investigating unusual forms of ice that can exist at room temperature when subjected to extreme pressure. Ice comes in many forms, even when made of nothing but water [...]
Nobel-winning, tiny ‘sponge crystals’ with an astonishing amount of inner space
The 2025 Nobel Prize in chemistry was awarded to Richard Robson, Susumu Kitagawa and Omar Yaghi on Oct. 8, 2025, for the development of metal-organic frameworks, or MOFs, which are tunable crystal structures with extremely [...]
Harnessing Green-Synthesized Nanoparticles for Water Purification
A new review reveals how plant- and microbe-derived nanoparticles can power next-gen water disinfection, delivering cleaner, safer water without the environmental cost of traditional treatments. A recent review published in Nanomaterials highlights the potential of green-synthesized nanomaterials (GSNMs) in [...]
Brainstem damage found to be behind long-lasting effects of severe Covid-19
Damage to the brainstem - the brain's 'control center' - is behind long-lasting physical and psychiatric effects of severe Covid-19 infection, a study suggests. Using ultra-high-resolution scanners that can see the living brain in [...]
CT scan changes over one year predict outcomes in fibrotic lung disease
Researchers at National Jewish Health have shown that subtle increases in lung scarring, detected by an artificial intelligence-based tool on CT scans taken one year apart, are associated with disease progression and survival in [...]
AI Spots Hidden Signs of Disease Before Symptoms Appear
Researchers suggest that examining the inner workings of cells more closely could help physicians detect diseases earlier and more accurately match patients with effective therapies. Researchers at McGill University have created an artificial intelligence tool capable of uncovering [...]
Breakthrough Blood Test Detects Head and Neck Cancer up to 10 Years Before Symptoms
Mass General Brigham’s HPV-DeepSeek test enables much earlier cancer detection through a blood sample, creating a new opportunity for screening HPV-related head and neck cancers. Human papillomavirus (HPV) is responsible for about 70% of [...]
Study of 86 chikungunya outbreaks reveals unpredictability in size and severity
The symptoms come on quickly—acute fever, followed by debilitating joint pain that can last for months. Though rarely fatal, the chikungunya virus, a mosquito-borne illness, can be particularly severe for high-risk individuals, including newborns and older [...]
Tiny Fat Messengers May Link Obesity to Alzheimer’s Plaque Buildup
Summary: A groundbreaking study reveals how obesity may drive Alzheimer’s disease through tiny messengers called extracellular vesicles released from fat tissue. These vesicles carry lipids that alter how quickly amyloid-β plaques form, a hallmark of [...]
Ozone exposure weakens lung function and reshapes the oral microbiome
Scientists reveal that short-term ozone inhalation doesn’t just harm the lungs; it reshapes the microbes in your mouth, with men facing the greatest risks. Ozone is a toxic environmental pollutant with wide-ranging effects on [...]
New study reveals molecular basis of Long COVID brain fog
Even though many years have passed since the start of the COVID-19 pandemic, the effects of infection with SARS-CoV-2 are not completely understood. This is especially true for Long COVID, a chronic condition that [...]
Scientists make huge Parkinson’s breakthrough as they discover ‘protein trigger’
Scientists have, for the first time, directly visualised the protein clusters in the brain believed to trigger Parkinson's disease, bringing them one step closer to potential treatments. Parkinson's is a progressive incurable neurological disorder [...]
Alpha amino acids’ stability may explain their role as early life’s protein building blocks
A new study from the Hebrew University of Jerusalem published in the Proceedings of the National Academy of Sciences sheds light on one of life's greatest mysteries: why biology is based on a very specific set [...]
3D bioprinting advances enable creation of artificial blood vessels with layered structures
To explore possible treatments for various diseases, either animal models or human cell cultures are usually used first; however, animal models do not always mimic human diseases well, and cultures are far removed [...]
Drinking less water daily spikes your stress hormone
Researchers discovered that people who don’t drink enough water react with sharper cortisol spikes during stressful events, explaining why poor hydration is tied to long-term health risks. A recent study in the Journal of Applied [...]
