The discovery of nanoparticles has significantly impacted many fields of science. Nanoparticles, with their unique properties due to their small size and large surface-area-to-volume ratio, have expanded the realms of possibility across sectors from clean energy to medicine.
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Nanoparticles can be arranged into thin layers to form nanofilms - a single-atom-thick layer on the surface of which physicochemical processes occur. This material is vastly gaining recognition as an increasing number of applications of nanofilms emerge, from displays and sensors to energy storage. Here, we discuss how nanofilms are being used to drive innovation in medicine, specifically in drug delivery and biomedical imaging.
The Use of Nanofilms in Drug Delivery
Nanoparticles have been important to pharmaceuticals for several decades, since the first nano-formulated drug, Doxil, entered the market in 1995. In the years that have followed, nanoparticles have been intensely researched in this field, which has helped to develop novel therapeutics for some of the most challenging diseases. In particular, nanoparticle-engineered drugs have been pivotal in the treatment of cancer, HIV-AIDS, and others.
Currently, there is much work in development exploring how nanoparticle thin films can be leveraged in drug delivery. Already, we have numerous examples of how nanoparticles can improve drug delivery by aiding the targeted and sustained delivery of therapeutic agents to exact biological targets. Thus facilitating controlled release therapy and decreasing drug-related toxicity. As a result of working with nanoparticles, scientists have been able to develop therapeutic systems to effectively deliver drugs to tissues in the body that may previously have been inaccessible.
Here, we look at recent research exploring the use of nanofilms in this area. For example, in 2019, researchers in China developed a nanoparticle thin film for the oral administration of cancer treatment. In their film, they used graphene as a nanocarrier alongside the anticancer drug pingyangmycin (PYM).
The film was constructed with poly(acrylic acid)-cysteine (PAA-cys) to help the drug delivery system adhere to the mucus layer of the small intestine, thus enabling drug bioavailability. The PAA-cys and poly(allylamine hydrochloride) (PAH) were also cross-linked on the surface of the film to help protect the nanocarrier and drug from demise from the gastric acids, enabling safe delivery to the intestine, its destination to release the drug.
The results showed that the system facilitated drug release at a lower pH, showing the potential of the system to effectively deliver drugs to tumor tissue (an acidic environment) while limiting its impact on normal tissue.
Other studies have focused on the use of nanoparticle thin films that are stimuli-responsive for use in photothermal therapy as a potential cancer treatment (e.g. Lima-Sousa et al., 2020; Patil et al., 2021). Photothermal therapy leverages the ability of nanoparticles to convert near-infrared radiation (NIR) into vibrational energy, resulting in heat production - which kills cancer cells in areas where nanoparticles accumulate. The benefit of photothermal therapy is that it damages the cancerous cells by targeting the nanoparticles, without harming the healthy tissue it passes through on its way to reach the diseased tissue.
Graphene oxide has emerged as a reliable nanomaterial for use in films that are developed for use in this application. Graphene oxide can produce enough heat to kill cancer cells and does so more effectively than carbon nanotube-based films. By using graphene oxide, scientists can develop NIR-responsive thin films with drug-loading capabilities where graphene oxide serves a purpose as a structural component as well as a NIR-responsive material.
Nanofilms Can Enhance Biomedical Imaging
Nanoparticle thin films are also being used to enhance biomedical imaging techniques. Because of their incredibly small size, nanoparticles are an ideal candidate for oncology imaging, in particular, because they can accumulate in tumor locations with high probability. Compared to organic dyes, nanoparticles have more efficient fluorescence efficiency, resulting in high-contrast images. Finally, due to their high surface-area-to-volume ratio, nanoparticles can be adhered to tumor cells, making it easier to detect and image them.
So far, studies have shown that nanoparticle thin films can be used to improve fluorescent imaging, positron emission tomography (PET), and ultrasound techniques. Studies have shown that the layer-by-layer (LbL) technique can be used to produce graphene oxide-containing films that are useful in biomedical imaging.
A study by Choi et al. developed an extracellular matrix (ECM) nanofilm selectively condensed on a large pore-sized track-etched (TE) membrane. The film achieved enhanced optical clarity with scanning electron microscopy (SEM), visualizing intercellular interactions and transmigration of cells across the membrane, offering a platform to investigate various intercellular communications.
Finally, research by Shi et al. has demonstrated the potential to develop multifunctional nanomaterials that work both to enhance biomedical imaging as well as a theranostic agent. This work highlights the possibility of using a single material as a fluorescent marker with a dual function as a therapeutic component. In the future, we may see further research developing nanoparticle thin films to meet this potential dual application.
References and Further Reading
Choi, B. et al. (2021) “Condensed ECM-based nanofilms on highly permeable pet membranes for robust cell-to-cell communications with improved optical clarity,” Biofabrication, 13(4), p. 045020. https://doi.org/10.1088/1758-5090/ac23ad.
Lima-Sousa, R. et al. (2020) “Injectable in situ forming Thermo-responsive graphene based hydrogels for cancer chemo-photothermal therapy and NIR light-enhanced antibacterial applications,” Materials Science and Engineering: C, 117, p. 111294. https://doi.org/10.1016/j.msec.2020.111294.
Liu, Y. et al. (2019) “Oral delivery of pingyangmycin by layer-by-layer (LBL) self-assembly polyelectrolyte-grafted nano graphene oxide,” Journal of Nanoscience and Nanotechnology, 19(4), pp. 2260–2268. https://doi.org/10.1166/jnn.2019.16531.
Markovic, Z.M. et al. (2011) “In vitro comparison of the photothermal anticancer activity of graphene nanoparticles and carbon nanotubes,” Biomaterials, 32(4), pp. 1121–1129. https://doi.org/10.1016/j.biomaterials.2010.10.030.
Oliveira, A.M. et al. (2022) “Graphene oxide thin films with drug delivery function,” Nanomaterials, 12(7), p. 1149. https://doi.org/10.3390/nano12071149.
Patil, T.V. et al. (2021) “Graphene oxide-based stimuli-responsive platforms for biomedical applications,” Molecules, 26(9), p. 2797. https://doi.org/10.3390/molecules26092797.
Rizvi, S.A.A. and Saleh, A.M. (2018) “Applications of nanoparticle systems in Drug Delivery Technology,” Saudi Pharmaceutical Journal, 26(1), pp. 64–70. https://doi.org/10.1016/j.jsps.2017.10.012.
Shi, S. et al. (2013) “Tumor vasculature targeting and imaging in living mice with reduced graphene oxide,” Biomaterials, 34(12), pp. 3002–3009. https://doi.org/10.1016/j.biomaterials.2013.01.047.
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