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
Researchers Reveal What Happens to Your Brain When You Don’t Get Enough Sleep
What if poor sleep was doing more than just making you tired? Researchers have discovered that disrupted sleep in older adults interferes with the brain’s ability to clean out waste, leading to memory problems [...]
How to prevent chronic inflammation from zombie-like cells that accumulate with age
In humans and other multicellular organisms, cells multiply. This defining feature allows embryos to grow into adulthood, and enables the healing of the many bumps, bruises and scrapes along the way. Certain factors can [...]
Breakthrough for long Covid patients who lost sense of smell
A breakthrough nasal surgery has restored the sense of smell for a dozen long Covid patients. Experts at University College London Hospitals NHS Foundation Trust successfully employed a technique typically used for correcting blocked nasal passages, [...]
Scientists Invent Plastic That Can Dissolve In Seawater In Just A Few Hours
Plastic waste and pollution in the sea have been among the most serious environmental problems for decades, causing immense damage to marine life and ecosystems. However, a breakthrough discovery may offer a game-changing solution. [...]
Muscles from the 3D printer
Swiss researchers have developed a method for printing artificial muscles out of silicone. In the future, these could be used on both humans and robots. Swiss researchers have succeeded in printing artificial muscles out [...]
Beneficial genetic changes observed in regular blood donors
Researchers at the Francis Crick Institute have identified genetic changes in blood stem cells from frequent blood donors that support the production of new, non-cancerous cells. Understanding the differences in the mutations that accumulate [...]
Shocking Amounts of Microplastics in the Brain – It Could Be Increasing Our Risk of Dementia
The brain has higher concentrations of plastic particles compared to other organs, with increased levels found in dementia patients. In a comprehensive commentary published in Brain Medicine, researchers highlight alarming new evidence of microplastic accumulation [...]
Baffling Scientists for Centuries: New Study Unravels Mystery of Static Electricity
ISTA physicists demonstrate that contact electrification depends on the contact history of materials. For centuries, static electricity has intrigued and perplexed scientists. Now, researchers from the Waitukaitis group at the Institute of Science and [...]
Tumor “Stickiness” – Scientists Develop Potential New Way To Predict Cancer’s Spread
UC San Diego researchers have developed a device that predicts breast cancer aggressiveness by measuring tumor cell adhesion. Weakly adherent cells indicate a higher risk of metastasis, especially in early-stage DCIS. This innovation could [...]
Scientists Just Watched Atoms Move for the First Time Using AI
Scientists have developed a groundbreaking AI-driven technique that reveals the hidden movements of nanoparticles, essential in materials science, pharmaceuticals, and electronics. By integrating artificial intelligence with electron microscopy, researchers can now visualize atomic-level changes that were [...]
Scientists Sound Alarm: “Safe” Antibiotic Has Led to an Almost Untreatable Superbug
A recent study reveals that an antibiotic used for liver disease patients may increase their risk of contracting a dangerous superbug. An international team of researchers has discovered that rifaximin, a commonly prescribed antibiotic [...]
Scientists Discover Natural Compound That Stops Cancer Progression
A discovery led by OHSU was made possible by years of study conducted by University of Portland undergraduates. Scientists have discovered a natural compound that can halt a key process involved in the progression [...]
Scientists Just Discovered an RNA That Repairs DNA Damage – And It’s a Game-Changer
Our DNA is constantly under threat — from cell division errors to external factors like sunlight and smoking. Fortunately, cells have intricate repair mechanisms to counteract this damage. Scientists have uncovered a surprising role played by [...]
What Scientists Just Discovered About COVID-19’s Hidden Death Toll
COVID-19 didn’t just claim lives directly—it reshaped mortality patterns worldwide. A major international study found that life expectancy plummeted across most of the 24 analyzed countries, with additional deaths from cardiovascular disease, substance abuse, and mental [...]
Self-Propelled Nanoparticles Improve Immunotherapy for Non-Invasive Bladder Cancer
A study led by Pohang University of Science and Technology (POSTECH) and the Institute for Bioengineering of Catalonia (IBEC) in South Korea details the creation of urea-powered nanomotors that enhance immunotherapy for bladder cancer. The nanomotors [...]
Scientists Develop New System That Produces Drinking Water From Thin Air
UT Austin researchers have developed a biodegradable, biomass-based hydrogel that efficiently extracts drinkable water from the air, offering a scalable, sustainable solution for water access in off-grid communities, emergency relief, and agriculture. Discarded food [...]
