Scientists have developed a DNA nanoflower that delivers chemotherapy and gene therapy directly to breast cancer cells, boosting effectiveness while reducing side effects in early tests.
Breast cancer continues to be one of the most prevalent cancers worldwide. Although drugs like Doxorubicin (DOX) are commonly used, their effectiveness is often limited by toxicity, poor targeting, and the development of multi-drug resistance. DNA nanostructures, due to their biocompatibility and programmability, are gaining attention as more precise delivery vehicles.
Researchers have created a new DNA nanoflower-based drug delivery system capable of co-delivering an antisense oligonucleotide (ASO) and the chemotherapy drug DOX.
Published in Micro & Nano Letters, the study demonstrates how they used a dual amplification method to form a flower-shaped DNA nanostructure with a high drug-loading capacity and highly targeted delivery.
This study focuses on tackling the limitations of traditional DOX-based therapies by combining gene silencing and chemotherapy into one delivery system. The DNA nanoflowers are also functionalised with AS1411, an aptamer that binds to nucleolin (a protein overexpressed on many tumour cells), improving targeting accuracy.
Building the DNA Nanoflower
The research team used a two-step amplification process to construct the nanoflowers. First, they used rolling circle amplification with Phi29 DNA polymerase to produce long single-stranded DNA sequences with repeating units. These sequences were then further amplified using multiplexed enzyme amplification, forming the unique nanoflower structure.
Specific sequences were engineered into the DNA scaffold to carry both the ASO and DOX drugs. ASO targeted PLK1, a gene associated with cancer cell growth and division, while DOX was intercalated directly into the DNA structure, making use of its natural affinity for DNA bases.
The AS1411 aptamer was conjugated to the nanostructure to enable tumour-specific targeting. The team confirmed the structure’s size, morphology, and successful functionalisation using a range of analytical techniques, including transmission electron microscopy, dynamic light scattering, and gel electrophoresis.
In Vitro and In Vivo Testing
In vitro experiments were carried out using MCF-7 breast cancer cells to assess cellular uptake, gene silencing, cytotoxicity, apoptosis, and cell migration. The researchers used flow cytometry, CCK-8 assays, qRT-PCR, western blotting, and Transwell migration assays to evaluate these parameters.
The in vivo phase of the study used nude mice implanted with MCF-7 cells to form breast tumours. Once tumours had developed, mice were treated locally with the nanoflower formulations.
Promising Results in Early Tests
Analysis of the DNA nanoflowers showed their high drug-loading efficiency and their uniform, flower-like shape. The aptamer-functionalised structures showed significantly enhanced uptake in cancer cells compared to non-targeted controls.
In lab tests, the nanoflower carrying both ASO and DOX (referred to as DNF-ASO@DOX) reduced tumour cell proliferation and triggered apoptosis more effectively than either DOX or ASO alone. The ASO silenced PLK1 expression, confirmed at both the mRNA and protein levels, and resulted in cell cycle arrest and increased cell death.
The system allowed for controlled drug release in response to enzymatic signals, specifically FEN1, which is overexpressed in tumour cells. This meant the active agents were mainly released at the tumour site, minimising damage to healthy tissue.
In animal studies, tumours treated with DNF-ASO@DOX showed markedly reduced growth. Tissue analysis revealed higher levels of apoptosis and lower PLK1 expression in tumour cells. Blood tests and organ inspections indicated minimal systemic toxicity, supporting the biocompatibility of the nanoflower platform.
Looking Ahead
The study highlights the potential of DNA nanoflowers as a new kind of combination therapy tool, able to deliver both genetic and chemotherapeutic treatments in a highly targeted way. With its tumour-specific binding and controlled release mechanisms, the platform could offer a new route to overcome issues like multi-drug resistance and off-target side effects that currently limit breast cancer treatments.
Journal Reference
Shen X., Zhu A., et al. (2025). DNA Nanoflower Enables Controlled Co-Delivery of Antisense Oligodeoxynucleotide and Doxorubicin for Anti-Breast Cancer Treatment. Micro & Nano Letters. DOI: 10.1002/mnnl.202500008, https://ietresearch.onlinelibrary.wiley.com/doi/10.1049/mna2.70008
News
Very low LDL-cholesterol correlates to fewer heart problems after stroke
Brigham and Women's Hospital's TIMI Study Group reports that in patients with prior ischemic stroke, very low achieved LDL-cholesterol correlated with fewer major adverse cardiovascular events and fewer recurrent strokes, without an apparent increase [...]
“Great Unified Microscope” Reveals Hidden Micro and Nano Worlds Inside Living Cells
University of Tokyo researchers have created a powerful new microscope that captures both forward- and back-scattered light at once, letting scientists see everything from large cell structures to tiny nanoscale particles in a single shot. Researchers [...]
Breakthrough Alzheimer’s Drug Has a Hidden Problem
Researchers in Japan found that although the Alzheimer’s drug lecanemab successfully removes amyloid plaques from the brain, it does not restore the brain’s waste-clearing system within the first few months of treatment. The study suggests that [...]
Concerning New Research Reveals Colon Cancer Is Skyrocketing in Adults Under 50
Colorectal cancer is striking younger adults at alarming rates, driven by lifestyle and genetic factors. Colorectal cancer (CRC) develops when abnormal cells grow uncontrollably in the colon or rectum, forming tumors that can eventually [...]
Scientists Discover a Natural, Non-Addictive Way To Block Pain That Could Replace Opioids
Scientists have discovered that the body can naturally dull pain through its own localized “benzodiazepine-like” peptides. A groundbreaking study led by a University of Leeds scientist has unveiled new insights into how the body manages pain, [...]
GLP-1 Drugs Like Ozempic Work, but New Research Reveals a Major Catch
Three new Cochrane reviews find evidence that GLP-1 drugs lead to clinically meaningful weight loss, though industry-funded studies raise concerns. Three new reviews from Cochrane have found that GLP-1 medications can lead to significant [...]
How a Palm-Sized Laser Could Change Medicine and Manufacturing
Researchers have developed an innovative and versatile system designed for a new generation of short-pulse lasers. Lasers that produce extremely short bursts of light are known for their remarkable precision, making them indispensable tools [...]
New nanoparticles stimulate the immune system to attack ovarian tumors
Cancer immunotherapy, which uses drugs that stimulate the body’s immune cells to attack tumors, is a promising approach to treating many types of cancer. However, it doesn’t work well for some tumors, including ovarian [...]
New Drug Kills Cancer 20,000x More Effectively With No Detectable Side Effects
By restructuring a common chemotherapy drug, scientists increased its potency by 20,000 times. In a significant step forward for cancer therapy, researchers at Northwestern University have redesigned the molecular structure of a well-known chemotherapy drug, greatly [...]
Lipid nanoparticles discovered that can deliver mRNA directly into heart muscle cells
Cardiovascular disease continues to be the leading cause of death worldwide. But advances in heart-failure therapeutics have stalled, largely due to the difficulty of delivering treatments at the cellular level. Now, a UC Berkeley-led [...]
The basic mechanisms of visual attention emerged over 500 million years ago, study suggests
The brain does not need its sophisticated cortex to interpret the visual world. A new study published in PLOS Biology demonstrates that a much older structure, the superior colliculus, contains the necessary circuitry to perform the [...]
AI Is Overheating. This New Technology Could Be the Fix
Engineers have developed a passive evaporative cooling membrane that dramatically improves heat removal for electronics and data centers Engineers at the University of California San Diego have created an innovative cooling system designed to greatly enhance [...]
New nanomedicine wipes out leukemia in animal study
In a promising advance for cancer treatment, Northwestern University scientists have re-engineered the molecular structure of a common chemotherapy drug, making it dramatically more soluble and effective and less toxic. In the new study, [...]
Mystery Solved: Scientists Find Cause for Unexplained, Deadly Diseases
A study reveals that a protein called RPA is essential for maintaining chromosome stability by stimulating telomerase. New findings from the University of Wisconsin-Madison suggest that problems with a key protein that helps preserve chromosome stability [...]
Nanotech Blocks Infection and Speed Up Chronic Wound Recovery
A new nanotech-based formulation using quercetin and omega-3 fatty acids shows promise in halting bacterial biofilms and boosting skin cell repair. Scientists have developed a nanotechnology-based treatment to fight bacterial biofilms in wound infections. The [...]
Researchers propose five key questions for effective adoption of AI in clinical practice
While Artificial Intelligence (AI) can be a powerful tool that physicians can use to help diagnose their patients and has great potential to improve accuracy, efficiency and patient safety, it has its drawbacks. It [...]
