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Targeting the Powerhouse of the Cell to Fight Cancer

Everyone knows that cancer as a disease is awful, but the side effects of currently utilized chemotherapies have their own horrors. Research into natural products as therapies have found some promising compounds, but they face barriers to practical use in patients. One particular molecule, artesunate (ART), recently showed high potential for anticancer activity when in the presence of iron. Unfortunately, ART has major problems that limit its current applicability, including low solubility in water and high instability in biologically relevant conditions.

One approach to get around these issues is to encapsulate the drug (pun intended) in a nanoparticle-based carrier. A carrier with a hydrophobic interior and hydrophilic exterior can bring higher concentrations of drugs with low solubility into a cell and protect them from deleterious conditions in the body. An additional benefit is the relative ease of incorporating targeting ligands into the particles during synthesis. This allows the drugs to only interact with specific cells or, in this specific case, the mitochondria within cells.

Figure 1. Schematic of the nanoparticle synthesis process complete with targeting ligand molecules. The anticancer agent is activated in the presence of iron.

Researchers in China have prepared approximately 200 nm nanoparticle carriers for ART (Figure 1) using triphenyl phosphonium (TPP) as a mitochondrial targeting ligand. These nanoparticles remained stable in biologically relevant conditions for a week, sufficient for in-vitro studies. The studies showed significant decreases in cancer cell growth when the nanoparticles were used compared to the ART alone. The nanoparticles with TPP on the surface showed the highest efficacy, particularly when coupled with iron treatment to activate the ART.

Figure 2. Images of cells exposed to nanoparticles with (bottom) and without (top) a targeting ligand filled with different fluorescent dyes. The increased brightness corresponds to higher uptake of the nanoparticles by the cells.

To further investigate the cell uptake pathway of the nanoparticles, the researchers added fluorescent dye molecules to the inside of the particles. Once the cells took up and ruptured the nanoparticles, the dyes were released and became visible to the researchers (Figure 2). The fluorescence was twice as great in cells exposed to the nanoparticles treated with the TPP targeting ligand, showing its value for cell uptake. The researchers also used fluorescent dyes that react with reactive oxygen species (ROSs), as their generation is how ART kills cancer cells. The in-vitro studies showed an over three-fold increase in fluorescence from reactions with ROSs which, combined with data showing higher rates of cell death, supports the increased activity of ART when combined with this nanoparticle architecture.

To find out more please read:

A mitochondria targeting artesunate prodrug-loaded nanoparticle exerting anticancer activity via iron-mediated generation of the reactive oxygen species

Zhigang Chen, Xiaoxu Kang, Yixin Wu, Haihua Xiao, Xuzi Cai, Shihou Seng, Xuefeng Wang and Shiguo Chen

Chem. Commun., 2019, 55, 4781 – 4784.

About the blogger:

 

Beth Mundy is a PhD candidate in chemistry in the Cossairt lab at the University of Washington in Seattle, Washington. Her research focuses on developing new and better ways to synthesize nanomaterials for energy applications. She is often spotted knitting in seminars or with her nose in a good book. You can find her on Twitter at @BethMundySci.

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Using Carbon to Make a Better Solar Cell

Maybe I’m stating the obvious, but solar cells are incredibly complex devices with more components than just the light absorber.

While the focus on the active layer by chemists looking to develop new materials is understandable, in order to truly create next-generation solar cells the other components of the architecture must be improved.  Creating the crack-resistant or resilient layers necessary for functional flexible solar cells is a major challenge currently being addressed. These new materials and approaches also need to work within the general framework of fabrication techniques used for the other layers – ideally at low temperature and solution processible.

An often-neglected piece of the puzzle is the electrode. Electrodes are traditionally composed of a thin metal layer, which is often vapor deposited at high temperatures and low pressures. This class of electrodes is expensive, susceptible to degradation, and can damage the critical hole transport or active layers. One emerging alternative is carbon-based electrodes, applied as pastes. These low-cost, highly stable, and hydrophobic materials are attractive given their compatibility with emerging photovoltaic technologies, particularly perovskites. Their broad application has been limited by the necessity of toxic solvents to create the pastes, but researchers in China have developed a low-temperature, highly conductive carbon paste that can be screen printed onto perovskite solar cells without using toxic solvents.

Fabrication schematic and cross sectional SEM for a perovskite solar cell with a carbon electrode

Figure 1. (a) Fabrication schematic for perovskite solar cells with carbon electrodes and hole transport layers. (b) Cross sectional SEM image of a device.

Not only are the solvents more environmentally friendly compared to those previously used, they also increase the mechanical strength of the final film and, under fabrication conditions, do not damage the perovskite active layer or organic hole transport layer. While the hole transport layer isn’t strictly necessary to create a working device, it has been shown to increase the champion efficiency from 11.7% to 14.55%. This is likely due to poor contact between the perovskite and carbon electrode, which the thin hole transport layer (PEDOT:PSS) helps remedy.

Carbon-based electrode undergoing a bending test and sheet resistivity data

Figure 2. (a) A sample undergoing a bending test. (b) The electrode sheet resistance before and after 100 bends.

The most exciting aspect of these electrodes is their resilience when subjected to a bending test. After 100 bends, the researchers saw no visible film damage or increase in the sheet resistance when compared to the initial sample. Actual flexible solar cells fabricated and studied did show a decrease in performance after 1,000 bends, but this was attributed to known robustness issues in the base ITO layer. This work with carbon-based electrode materials could lead to simpler manufacturing for fabricating perovskite solar cells at a commercial level.

 

To find out more please read:

A low-temperature carbon electrode with good perovskite compatibility and high flexibility in carbon based perovskite solar cells

Shiyu Wang, Pei Jiang, Wenjian Shen, Anyi Mei, Sixing Xiong, Xueshi Jiang, Yaoguang Rong, Yiwen Tang, Yue Hu & Hongwei Han

Chem. Commun., 2019, 55, 2765-2768

This article is also part of the Chemical CommunicationsPerovskites‘ themed collection.

About the blogger:

 

Beth Mundy is a PhD candidate in chemistry in the Cossairt lab at the University of Washington in Seattle, Washington. Her research focuses on developing new and better ways to synthesize nanomaterials for energy applications. She is often spotted knitting in seminars or with her nose in a good book. You can find her on Twitter at @BethMundySci.

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