In an article recently published in the journal ACS Applied Bio Materials, researchers discussed the utility of neutrophil cell membrane coating of a self-assembly nanoconstruct to enable high specificity for triple-negative breast cancer treatment.
Severity of Breast Cancer
With a 12% lifetime risk for women, breast cancer (BC) continues to be the second most prevalent cancer diagnosed in women in the United States. The majority of treatment for advanced breast cancer, metastatic breast cancer, and triple-negative breast cancer (TNBC) is the systemic injection of chemotherapeutic drugs because there are relatively few foods and drug administration (FDA)-approved medicines for such aggressive forms of the disease. The survival rate of patients was dramatically increased by chemotherapy using cytotoxic drugs. However, because of their non-specific distribution, chemotherapy might cause side effects such as induced neutropenia, cardiotoxicity, peripheral neurotoxicity, and myelosuppression.
Nanotechnology in Medical Treatment
The development of medication delivery systems based on nanotechnology has made considerable advancements in overcoming traditional constraints. Drug delivery methods based on nanoparticles (NP) have significantly advanced the field of cancer treatment.
The reticular endothelial system (RES), which clears these exogenous materials despite their therapeutic benefits, prevents tumor penetration by generating subtherapeutic concentrations in combination with a dense extracellular matrix. The use of artificial cell membranes or cell membranes obtained from nature can be included in synthetic constructs or NPs using the biomimetic NP method, a novel type of nanoplatform.
Numerous Cell Membrane-Coated Nanoparticles
Numerous cell membrane-coated NPs using membranes from platelets and nucleated cells are described in the literature. According to literature findings, NPs with cell membrane (MEM) coatings already actively express their self-markers, enabling them to adhere to tumor cells and locations.
Biomimetic Nanoparticles for the Treatment of Triple Negative Breast Cancer
In this article, the authors discussed developing a biomimetic NP construct with NPs encased in cell membranes that demonstrated a particular affinity for triple-negative breast cancer cells. The team created biomimetic supramolecular nanoconstructs with a core made of poly(vinyl pyrrolidone)-tannic acid (PVP-TA NPs/PVT NPs) and biofunctionalized with neutrophil cell membranes (PVT-NEU NPs). A PVT-NEU NP construct was synthesized, described, and tested in vitro and in vivo for enhanced targeting and therapeutic effects.
The team discussed the possibility of biomimetic NPs as a promising therapeutic choice for targeted medication delivery for advanced-stage breast cancer and other diseases of a similar nature. The creation of a perfect neutrophil-cloaked NP supramolecular construct for improved tumor-targeted administration was described. To find a suitable membrane-cloaked NP construct, various cellular binding interactions, biological tests, and bio-distribution/tumor targeting investigations were demonstrated. An ectopic xenograft tumor, the MDA-MB-231 breast cancer mouse model, was used to confirm the superior anti-tumor efficacy of the neutrophil membrane-cloaked NP construct.
The researchers demonstrated that the inherent membrane features of the proposed NPs, which resulted in improved circulation, self-binding capacity, and recognition/targeting capabilities of the source cells, allowed for successful targeting and tumor delivery overall. Due to cell-specific binding, these nanostructures not only enhanced binding to the initial tumor site but also could target the metastatic tumor.
Biological Characteristics of PVP-TA NPs
The core of PVP-TA NPs coated with activated human neutrophil membranes was present, according to the analysis of PVT-NEU NPs. The study’s findings supported PVTNEU NPs’ increased targeting and engagement with tumor cells, which enhanced a model therapeutic agent’s therapeutic activity. In contrast to PVT NPs, PVT-NEU NPs showed pronounced binding to MDA-MB-231 and MDA-MB-468 cells, while breast epithelial cells, MCF10A, displayed very little internalization, indicating a preference for absorption in cancer cells as opposed to noncancer cells. PTX-loaded PVT NP treatment dramatically reduced the IC50 values compared to unloaded PTX.
Compared to PTX alone in MDA-MB-231, PTX-loaded PVT-NEU NPs demonstrated a substantial change of 2.95-fold reduction. When compared to PVT NPs, PVT-NEU NPs showed significantly greater tumor retention of the ICG dye after 72 hours. PTX solution demonstrated a 52% reduction in tumor growth compared to control mice.
The results of the SDS-PAGE Coomassie stain indicated that LFA-1, MAC-1, PSGL-1, and PECAM-1 could be present. Although PVT-NEU NPs appeared to have fewer proteins than NEU, the presence of membrane proteins showed that these proteins were properly translocated to the surface of PVT NPs. When the NPs were loaded with the fluorescent dye C6, there was a greater uptake of PVTNEU NPs than PVT NPs both intracellularly and in situ.
Conclusions and Future Perspectives
In conclusion, this study described the creation, improvement, and characterization of a biomimetic nanoconstruct that combined cell membrane properties and provided the NPs with a biological identity for treating breast cancer cells.
In a xenograft mouse model, neutrophil membrane-coated nanoconstructs showed tumor retention, enhanced cellular targeting, and relatively less biodistribution in healthy organs. PTX-loaded PVT-NEU NPs showed better anti-migratory, antiproliferative, and anti-colonogenic activities. Comparing this nanoconstruct to uncoated NPs and the natural drug paclitaxel, it decreased systemic toxicity, showed better in vivo therapeutic effect, and good hemocompatibility.
The authors stated that this method of biomimetic-designed nanoconstructs has promise as a drug delivery system with the potential for enhanced therapeutic outcomes, active tumor targeting, and fewer adverse effects compared to traditional chemotherapy for the treatment of breast cancer. They mentioned that the results of this study could be used to inform the design of experiments for the targeted drug delivery to the tumor site for additional disease models with comparable traits.
News
Antibiotic Breakthrough: Revolutionary Chinese Study Paves Way for Superbug Defeating Drugs
New research reveals that fluorous lipopetides act as highly effective antibiotics. Bacterial infections resistant to multiple drugs, which no existing antibiotics can treat, represent a significant worldwide challenge. A research group from China has [...]
Signs of Multiple Sclerosis Show Up in Blood Years Before Symptoms Appear
UCSF scientists clear a potential path toward earlier treatment for a disease that affects nearly 1,000,000 people in the United States. By Levi Gadye In a discovery that could hasten treatment for patients with multiple [...]
Advanced RNA Sequencing Reveals the Drivers of New COVID Variants
A study reveals that a new sequencing technique, tARC-seq, can accurately track mutations in SARS-CoV-2, providing insights into the rapid evolution and variant development of the virus. The SARS-CoV-2 virus that causes COVID has the unsettling [...]
No More Endless Boosters? Scientists Develop One-for-All Virus Vaccine
End of the line for endless boosters? Researchers at UC Riverside have developed a new vaccine approach using RNA that is effective against any strain of a virus and can be used safely even by babies or the immunocompromised. Every [...]
How Are Hydrogels Shaping the Future of Biomedicine?
Hydrogels have gained widespread recognition and utilization in biomedical engineering, with their applications dating back to the 1960s when they were first used in contact lens production. Hydrogels are distinguished from other biomaterials in [...]
Nanovials method for immune cell screening uncovers receptors that target prostate cancer
A recent UCLA study demonstrates a new process for screening T cells, part of the body's natural defenses, for characteristics vital to the success of cell-based treatments. The method filters T cells based on [...]
New Research Reveals That Your Sense of Smell May Be Smarter Than You Think
A new study published in the Journal of Neuroscience indicates that the sense of smell is significantly influenced by cues from other senses, whereas the senses of sight and hearing are much less affected. A popular [...]
Deadly bacteria show thirst for human blood: the phenomenon of bacterial vampirism
Some of the world's deadliest bacteria seek out and feed on human blood, a newly-discovered phenomenon researchers are calling "bacterial vampirism." A team led by Washington State University researchers has found the bacteria are [...]
Organ Architects: The Remarkable Cells Shaping Our Development
Finding your way through the winding streets of certain cities can be a real challenge without a map. To orient ourselves, we rely on a variety of information, including digital maps on our phones, [...]
Novel hydrogel removes microplastics from water
Microplastics pose a great threat to human health. These tiny plastic debris can enter our bodies through the water we drink and increase the risk of illnesses. They are also an environmental hazard; found [...]
Researchers Discover New Origin of Deep Brain Waves
Understanding hippocampal activity could improve sleep and cognition therapies. Researchers from the University of California, Irvine’s biomedical engineering department have discovered a new origin for two essential brain waves—slow waves and sleep spindles—that are critical for [...]
The Lifelong Cost of Surviving COVID: Scientists Uncover Long-Term Effects
Many of the individuals released to long-term acute care facilities suffered from conditions that lasted for over a year. Researchers at UC San Francisco studied COVID-19 patients in the United States who survived some of the longest and [...]
Previously Unknown Rogue Immune Key to Chronic Viral Infections Discovered
Scientists discovered a previously unidentified rogue immune cell linked to poor antibody responses in chronic viral infections. Australian researchers have discovered a previously unknown rogue immune cell that can cause poor antibody responses in [...]
Nature’s Betrayal: Unmasking Lead Lurking in Herbal Medicine
A case of lead poisoning due to Ayurvedic medicine use demonstrates the importance of patient history in diagnosis and the need for public health collaboration to prevent similar risks. An article in CMAJ (Canadian Medical Association [...]
Frozen in Time: How a DNA Anomaly Misled Scientists for Centuries
An enormous meteor spelled doom for most dinosaurs 65 million years ago. But not all. In the aftermath of the extinction event, birds — technically dinosaurs themselves — flourished. Scientists have spent centuries trying [...]
‘Mini kidneys’ reveal new insights into metabolic defects in polycystic kidney disease
Scientists at Nanyang Technological University, Singapore (NTU Singapore) have successfully grown 'mini kidneys' in the lab and grafted them into live mice, revealing new insights into the metabolic defects and a potential therapy for [...]