In an article recently published in the open-access MDPI journal nanomaterials, researchers investigated the mechanism of interaction between nanoscale materials and specific cells for biomedical applications, primarily related to targeted delivery and tracing.
Here, the localization, cellular uptake quantity, and response time of gold nanorods in MCF-7 and SKBR-3 breast cancer cells were measured.
Background
The amalgamation of biotechnology and nanotechnology has been a quite fascinating field of research for the last few years.
Currently, nanomaterials are extensively used in biomedical applications such as drug delivery, magnetic or fluorescent bio-imaging, tissue engineering, tracing pathogens in sensitive organs, cancer chemotherapy, and many more. However, each nanomaterial interacts differently with a particular type of cell.
Many studies have shown cellular uptake of gold nanorods by cancer cells. MCF-7 and SKBR-3 cancer cell lines represent HER2-negative and HER2-positive breast cancer models, respectively. These cells intake gold nanorods through a mechanism occurring at the surface of the cell membrane, called endocytosis.
Inductively coupled plasma mass spectrometry (ICP-MS) can measure the efficiency of targeted delivery and cellular uptake of these nanoparticles, while transmission electron microscopy (TEM) can be used to investigate their localization.
Figure 1. Transmission electron microscope images of gold nanorods with aspect ratio around 3 at different magnifications (a–c). (d) UV–visible spectrum analysis of the prepared gold nanorods showing longitudinal and transverse plasmons around 690 nm and 514 nm, respectively. © White, B., White, M., Nima Alsudani, Z., Watanabe, F., Biris, A., Ali, N., (2022)
About the Study
In this article, researchers investigated the interaction mechanism of gold nanorods (Au NRs) in two types of breast cancer cell lines namely, MCF-7 and SKBR-3. More than 200 Au NRs with an average length and diameter of 36 and 12 nm, respectively, were synthesized using the silver ion-assisted seed-mediated method. Subsequently, MCF-7 and SKBR-3 cells were cultured in a conducive medium and allowed to bind with different concentrations of Au NRs for 1 and 2 days.
The excess Au NRs were washed away from the treated cancels using phosphate buffer saline (PBS) solution followed by treating with the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) reagent. Finally, ICP-MS and TEM analyses were performed to investigate the interaction mechanism.
Figure 2. TEM images of AuNRs in SKBR-3 cells at different time points and concentrations. SKBR-3 cells were treated with 5, 25, and 75 μg/mL of AuNRs for 1, 4, 24, and 48 h. Internalization of nanorods was observed starting at 4hourincubation with 75 μg/mL (a). After 24hourof incubation, internalization was observed with the 25 μg/mL (b) and 75 μg/mL concentrations (c). For cells incubated for 48 h, we observed internalization with 5, 25, and 75 μg/mL concentrations (d, e, and f, respectively). Red arrows point to gold nanorods localized in SKBR-3 cells. Electron photomicrographs shown are representative of at least three independent experiments with similar conditions. © White, B., White, M., Nima Alsudani, Z., Watanabe, F., Biris, A., Ali, N., (2022)
Observations
TEM images showed Au NRs had longitudinal and transverse plasmon resonances at around 680 and 514 nm, respectively. The average zeta potential of the NRs was −47.18 ± 4.26 mV. Au NRs did not show any cytotoxicity in healthy human cells. MTT methods indicated that the MCF-7 cells were less sensitive to Au NR exposure than the SKBR-3 cells for longer exposure times at higher concentrations. The SKBR-3 cells exhibited a drop in cell vitality due to higher sensitivity, whereas the MCF-7 cells had almost no drop in cell viability.
Both types of cells demonstrated a different pattern in cellular uptake of Au NRs for different exposure times and concentrations. The SKBR-3 cells had a constant cellular uptake between one to four hours, but 25 μg/mL Au NRs concentration had a higher uptake than the 75 μg/mL sample, i.e. lower concentration had a higher cellular uptake. In contrast, in MCF-7 cells, the 75 μg/mL AuNR-treated cell samples exhibited higher cellular uptake than 5 and 25 μg/mL samples, i.e. higher concentration samples had higher cellular uptake than lower concentration samples.
Furthermore, TEM analysis showed that the Au NRs interacted with the cell membrane of both cancer cells starting from one to 48 hours of exposure time. However, the Au NRs entered into the cell (i.e. internalized) for the samples with concentrations of 25 and 75 μg/mL. The 5 μg/mL concentration samples were never internalized. Moreover, the minimum exposure time for internalization was one hour and four hours for the MCF-7 and SKBR-3 cells, respectively.
The mechanism for the cellular uptake of the Au NRs was primarily micropinocytosis instead of receptor-mediated endocytosis. These Au NRs-carrying macropinosomes further interacted with the lysosomes inside the cells.
Figure 3. TEM images showing localization of gold nanorods in macropinosomes and lysosomes in both SKBR-3 and MCF-7 cell lines. AuNR localization in (a) macropinosomes (MA) and (b) lysosomes (Ly) of SKBR-3 cells. (c) Macropinosomes (MA) containing gold nanorods in MCF-7 and (d) lysosomes (Ly) containing gold nanorods in MCF-7. Red arrows point out macropinosomes and lysosomes containing gold nanorods in each image. Electron photomicrographs shown are representative of at least three independent experiments with similar conditions. © White, B., White, M., Nima Alsudani, Z., Watanabe, F., Biris, A., Ali, N., (2022)
Conclusions
To conclude, the researchers of this study investigated the interaction of Au NRs in two types of breast cancer cell lines, i.e. MCF-7 and SKBR-3. The shape, size, and zeta potential of Au NRs had different effects on cell vitality and toxicity of different cancer cells. Additionally, both cell types had different patterns of cellular uptake for Au NRs at different concentrations and exposure times.
The Au NRs did not enter into the cancer cells for samples with lower concentrations of NRs or lower exposure time. Also, the cellular uptake mechanism was primarily driven by micropinocytosis. These findings will help improve biomedical applications related to targeted drug delivery, tracing, and bio-imaging involving nanomaterials.
News
Scientists study lipids cell by cell, making new cancer research possible
Imagine being able to look inside a single cancer cell and see how it communicates with its neighbors. Scientists are celebrating a new technique that lets them study the fatty contents of cancer cells, [...]
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 [...]