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
A sceptical guide to AI agents in drug discovery
In conversation with Dr Eric Ma, Senior Principal Data Scientist at Moderna, Dr Raminderpal Singh examines what AI agents are actually good for, where the lock-in hides and why expertise has become more valuable [...]
Study identifies new targets for antiviral drugs against coronaviruses
A study led by researchers at the University of California San Diego School of Medicine and University of California, Riverside (UCR) School of Medicine has identified new targets for antiviral drugs against coronaviruses, including [...]
“Nearly Everybody Had Given Up” – Scientists Finally Solve a 60-Year Chemistry Mystery
After more than six decades of failed attempts, chemists have achieved a breakthrough involving a class of molecules long considered too unstable to isolate. Chemists have succeeded in isolating a group of molecules that [...]
Depression Symptoms Improved in Just 48 Hours After a Single Psychedelic Dose
A single dose of psilocybin produced rapid antidepressant effects in a small Swedish clinical trial, with improvements lasting for weeks. A single dose of psilocybin, the psychedelic compound found in magic mushrooms, produced rapid [...]
GHCE Concept
From the preface of the book Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artificial Intelligence, Edited by Frank Boehm: Since the publication of my first book (Nanomedical Device and Systems [...]
Human Bodies Are Producing Two Billion Tons of CO2 a Year
A new study reveals that the amount of carbon dioxide produced by human metabolism has increased dramatically over three decades. The carbon dioxide produced by human bodies as they convert food into energy increased [...]
A Hidden DNA Mechanism Could Explain How 20% of Human Cancers Develop
Researchers have identified an unexpected molecular vulnerability in cancers carrying BAF mutations. Mutations found in roughly 20% of human cancers may promote tumor growth by changing how DNA is organized inside cells. Researchers have [...]
Ebola kills over 5,300 in fastest-growing outbreak on record
Africa’s latest Ebola outbreak has killed nearly 5,400 people, the vast majority of them in the Democratic Republic of Congo (DRC), according to the continent’s top health agency. Africa Centres for Disease Control and [...]
China makes early progress in using sound waves to stimulate damaged brains
Chinese researchers are testing whether focused ultrasound can help restore consciousness in patients with severe brain injuries, adding to a growing international effort to use sound waves to stimulate deep brain structures without surgery. [...]
Micro-drones fly through the body thanks to ultrasound
At the EPFL, micro-drones have been developed that can be moved without a motor or battery.No motors, no batteries, no electronics on board, just small cavities that convert sound waves into thrust: this is [...]
A Single Enzyme Could Hold the Key to Treating a Devastating Brain Disorder
Blocking an enzyme’s production restored brain growth and healthy behaviors in mice engineered to develop Angelman syndrome, pointing to a possible treatment target. Children with Angelman syndrome begin to show difficulties with thinking and [...]
Scientists Develop a Clever New Way To Kill Cancer Cells From the Inside
Scientists have developed an experimental strategy that exploits a chemical byproduct of cancer cells to produce anticancer drugs directly inside them. Scientists in Japan have developed an experimental method that uses a chemical produced [...]
Our books are available worldwide!
Online Sellers other than Amazon, Routledge, and IOPP Indigo Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artifcial Intelligence Global Health Care Equivalency In The Age Of Nanotechnology, Nanomedicine And Artificial [...]
After only a short training, people in a coma managed to send targeted signals
Researchers have succeeded in communicating with brain-injured patients who are unconscious. They see enormous potential in this for future treatments. Patients who lie motionless in bed after a severe brain injury and do not [...]
MIT Scientists Reprogram Immune Cells Inside the Body To Destroy Cancer
Natural killer cells reprogrammed inside mice eliminated lymphoma tumors and helped damaged livers heal, though whether this approach could help people with cancer or autoimmune disease remains unknown. To make a cancer treatment from [...]
Melanoma mRNA Vaccine Shows Promise in Preventing Disease Recurrence
Key takeaways: Phase 3 trial finds personalized intismeran plus pembrolizumab may better prevent high-risk melanoma recurrence after surgery The trial enrolled 1,137 patients and builds on phase 2 results showing about half the recurrence [...]
