Hybrid nanoparticles to target cancer cells
NCCR Bio-Materials researchers from the Adolphe Merkle Institute (AMI) have developed a method that could help circumvent drug resistance in certain types of cancer. Using ultraviolet light and hybrid stimuli-responsive nanoparticles, the scientists were able to accelerate cell death in melanoma cells.
Nanomedicine is one of the most widely anticipated uses of nanotechnology, especially for the purposes of drug delivery and cancer therapy. Nanoparticles (NPs), with advanced functionalities such as stimuli-responsiveness and targeting moieties on the surface, can in theory be concentrated more easily in diseased cells while generating fewer side effects than traditional drugs. Due to their small size, they can also reach a wide range of cellular and intracellular targets. Because of these various factors, NPs are considered promising candidates to help overcome drug resistance in cancer therapy.
One approach that exploits stimuli-responsive NPs for cancer treatment is hyperthermia, which uses magnetic fields, light, radio waves, or ultrasound to induce a temperature increase inside cells or tissues. At the right temperature, cell death (apoptosis) can be provoked. The NCCR researchers considered one specific approach that targets melanoma cells, in which NPs then accumulate inside the cells’ lysosomal compartments. Lysosomes are sometimes called the “trash bag” of the cell, as they are responsible for degrading molecules and recycling their components. If these organelles leak, the cell will often die as a result. As this approach involves a physical process rather than a chemical one, there is no risk of the cells building up a resistance against it.
For human biomedical applications, however, NPs must be both biocompatible and safe, while demonstrating low persistence in the organism. The AMI scientists chose to investigate polydopamine (PDA), which is derived from melanin, a natural pigment found in human skin. First discovered in mussels, PDA is also found in many other organisms in nature. Besides being an adhesive, the polymer also converts UV radiation energy into heat, making it an interesting candidate for hyperthermia treatments.
The AMI researchers demonstrated that combining PDA with transferrin, a protein, affords hybrid nanoparticles that can latch onto certain types of cancer cells, which express an abundance of the required receptor, before passing through the cell membrane to finally reach the lysosomes. The method was tested in vitro on melanoma cells. After the cells were exposed to the NPs in a cell culture, the researchers were able to induce apoptosis by irradiating them with spatially focused ultraviolet light. They found a local induction of cell apoptosis induces lysosome membrane permeability.
“These results suggest that by delivering NPs to the lysosomes in targeted cancer cells this way, we can effectively kill the melanoma cells by inducing apoptosis,” explains NCCR Principal Investigator Professor Barbara Rothen-Rutishauser. “We have succeeded in developing a highly adaptable system to target cancer cells that could eventually be used as a treatment.”
Because both PDA and proteins are biocompatible, Rothen-Rutishauser believes that the system is unlikely to cause harm in organisms, although this will have to be validated by in vivo experimentation. “Our inexpensive and straightforward method for combining PDA with protein-based targeting functionality provides a suitable base to pursue investigations into the use of phototherapy, since NPs can be easily tailored to suit specific tasks.”
Reference: Hauser, D.; Estermann, M.; Milosevic, A.; Steinmetz, L.; Vanhecke, D.; Septiadi, D.; Drasler, B.; Petri-Fink, A.; Ball, V.; Rothen-Rutishauser, B. Polydopamine/Transferrin hybrid nanoparticles for targeted cell-killing, Nanomaterials, 2018, 8, 1065.