Scanning probe microscopy stands as an essential tool of nanotechnology, facilitating the examination of physical properties at scales as minute as the subatomic. Among these techniques, the Atomic Force Microscope and its variants have emerged as pivotal tools, enabling researchers to explore the complexities of atomic and molecular structures across various disciplines.
The AFM operates on the principle of detecting forces between a fine tip and a sample, offering extraordinary resolution and versatility in imaging endless materials, including non-conductive and soft specimens. Since its inception in 1986, significant improvements have been made in imaging thin films, crucial for understanding material properties at the nanoscale.
One notable advancement in AFM technology is the advent of low-temperature operation, which has revolutionized high-resolution measurements by mitigating thermal drift and noise, thereby enhancing imaging capabilities.
The pursuit of low-temperature AFM has led to the development of innovative instruments and methodologies aimed at achieving unparalleled resolution and stability. Cryogenic setups, employing flow cryostats or helium refrigeration systems, enable AFM operation at temperatures as low as 7 mK, opening new frontiers in material characterization and manipulation. However, the quest for high-resolution measurements at low temperatures poses challenges, including mechanical vibrations and spatial constraints within cryostats.
In the field of cancer treatment, LT-AFM plays a pivotal role in studying the behavior of nanoparticles and nanomaterials, which hold promise for delivering drugs directly to cancer cells or enhancing the effectiveness of radiation therapy. Biophysical studies facilitated by LT-AFM allow researchers to investigate biological molecules like proteins and DNA at the nanoscale, offering insights into cancer development and progression mechanisms.
In a recent study, the NanoMagnetics Instruments ezAFM was utilized in the production of a new method for cancer biomarker detection using graphene oxide screen electrodes (GPHOXE) with deactivated Cas9 (dCas9) proteins and synthetic guide RNA (sgRNA) (1). Because the surface of the graphene oxide screen electrodes is within the nanoscale, researchers were able to utilize AFM technology to observe the various changes in the surface when the deactivated proteins, as well as the synthetic guide RNA, were incorporated during the study. By being able to visualize the structural changes of the electrode based on the added material, the researchers were able to make sure that the resultant biosensor would indeed be able to correctly detect circulating tumor DNA.
Moreover, LT-AFM contributes to drug development by elucidating the interactions between drugs and biological molecules at the nanoscale. Characterizing drug binding to target molecules and studying their effects on cancer cell behavior provides crucial information for the development of novel cancer therapies.
For example, the NanoMagnetics Instruments ezAFM was utilized once again in a study related to the delivery of the histone deacetylase inhibitor CH-1521 in breast cancer treatment. The study focused on utilizing starch nanoparticles as a way of delivering the treatment to the target tumor tissues. Once the nanoparticles with the drugs were prepared, their morphological analysis was done through the use of AFM technology, which enabled the researchers to make sure that the morphological characteristics of the carrier nanoparticles were optimized for the delivery of the treatment (2).
The ezAFM was also utilized in the development of new methods to combat cancer, where in a recent study published in 2023, researchers studied the effects of attaching olive leaf extract onto chitosan nanoparticles (CNPs) in regards to their cytotoxicity against lung and breast cancer cells (3). Through the use of AFM technology, the researchers were able to once again characterize the physicochemical properties of the resultant nanoparticles, which was a key component in understanding their potential applications for future cancer treatments.
Ambient and low-temperature AFM represent indispensable tools for exploring the nanoworld, enabling researchers to clear up the mysteries of atomic and molecular systems. As technology advances and methodologies advance, the frontier of nanoscience continues to expand, promising exciting discoveries and transformative innovations on the horizon.
In conclusion, AFM – whether at room temperature or deep freeze – is more than just a tool. It's a window into a world that's both infinitely small and infinitely fascinating. While we have come a long way in understanding the ways in which the nanoworld works, we’ve still got a lot to learn. And as we continue to push the boundaries of nanoscience, who knows what incredible discoveries lie ahead?
References
1) Zihni Onur Uygun, Levent Yeniay, Ferhan Gi̇rgi̇n Sağın, CRISPR-dCas9 powered impedimetric biosensor for label-free detection of circulating tumor DNAs, Analytica Chimica Acta, Volume 1121, 2020, Pages 35-41, ISSN 0003-2670, https://doi.org/10.1016/j.aca.2020.04.009.
2) Alp, E., Damkaci, F., Guven, E., & Tenniswood, M. (2019). Starch nanoparticles for delivery of the histone deacetylase inhibitor CG-1521 in breast cancer treatment. International Journal of Nanomedicine, 14, 1335–1346. https://doi.org/10.2147/IJN.S191837
3) Özdamar, B., Sürmeli, Y., & Şanlı-Mohamed, G. (2023). Immobilization of olive leaf
extract with chitosan nanoparticles as an adjunct to enhance cytotoxicity. ACS Omega, 8(32), 28994–29002. https://doi.org/10.1021/acsomega.3c01494
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