Rupturing cancer cells by the expansion of functionalized stimuli-responsive hydrogels

Using particles with different functionalities for treating cancer has many advantages over other methods (for example, better access to remote parts of the body); however, current chemical (for example, chemotherapy) and biological (for example, immunotherapy) methods still face many challenges. Here, we describe a fundamentally different approach: using the physical force of an expanding stimuli-responsive hydrogel to rupture cancer cells attached on its surface. Specifically, we coated temperature-responsive hydrogels with a layer of cell-adherent arginine-glycine-aspartate (RGD) peptides. The approach involved first allowing cancer cells to attach onto the surface of the hydrogels, and then applying a change in temperature. As the hydrogel underwent a chemical transformation and expanded due to the stimulus, the cancer cells attached to it ruptured. The results from staining the cells with trypan blue, observing them using SEM, and analyzing them using the MTT assay showed that both breast and lung cancer cells died after the hydrogel expanded; hence, we showed that this physical force from the expanding hydrogel is strong enough to rupture the cancer cells. In addition, the force derived from the expanding hydrogel was determined separately to be larger than that needed to rupture typical cells. This physical approach is conceptually simple, technically easy to implement, and potentially generalizable for rupturing a wide range of cells. A hydrogel that uses physical force rather than drugs or radiation to kill breast and lung cancer cells has been developed. The approach by Siowling Soh at the National University of Singapore and colleagues exploits the temperature responsiveness of soft, watery polymers known as poly(N-isopropylacrylamides). The researchers coated the hydrogel with cell-adhering arginine-glycine-aspartate peptides, using a dopamine and lysine co-polymer to anchor the biomolecules. After seeding cancer cells onto the peptide-coated hydrogel, they dropped sample temperatures from 37°C to 22°C. The hydrogel expanded due to a phase transition, providing a force large enough to rupture the cancer cells attached to the surface — an easy-to-implement strategy effective for particles made of these coated hydrogels with sizes ranging from micrometers to millimeters. Measurements revealed the hydrogels can apply enough force to rupture a variety of cell types. Using functionalized particles for treatment of cancer is advantageous because they can access remote parts of the body and is minimally invasive. However, current chemical and biological methods still face challenges. A novel approach that uses the physical force of stimuli-responsive hydrogels is introduced. Temperature-responsive hydrogels were coated with cell-adherent molecules. After attaching cancer cells on its surface and changing the temperature, the force of the expanding stimuli-responsive hydrogel ruptures the cells. Comparing to other chemical and biological methods, this physical approach may be conceptually simpler, technically easier to implement, and more general for different types of cancer cells.