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

Abstract

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.

Fabrication and evaluation of a γ-PGA-based self-assembly transferrin receptor-targeting anticancer drug carrier

“…The efficacies of major antitumor chemical drugs in the clinic were hindered due to the short half-life, nonselective delivery approaches, and side effects. [43][44][45][46][47] Enormous challenges have been encountered in tumor treatment, and one of these is enhancement of the efficacy by site-specific drug delivery. The usage of targeting drug carrier for cancer treatment based on specific protein markers presenting in tumor tissues is one of the research highlights.…”

Hydrogels and Their Applications in Targeted Drug Delivery

“…The paper discussed experiments performed to confirm firmness of the RGD peptides with the cells (ex: MDAMB21) and their rupture using external heat stimulation. Since in vivo conditions in tumors normally produce a higher temperature than the surrounding areas, and also that it has been proved that the physical force generated from the expansion of the cells when they were heated was sufficient to kill them, that type of thermally responsive hydrogels proved to be highly advantageous options for achieving targeted cell killing [28].…”

“…Schematic depiction of the surface modification of hydrogel. The first layer of coating was polydopamine (PDA) and poly-L-lysine (PLL) followed by a layer of RGD peptides for binding cancer cells (reprinted (adapted) from[28]; the article is open access and the content reusable. Creative Commons International License 4.0 for the article is available in https://creativecommons.…”

“…Creative Commons International License 4.0 for the article is available in https://creativecommons. org/licenses/by/4.0/)[28].…”

Hydrogels and Their Applications in Targeted Drug Delivery

“…The paper discussed experiments performed to confirm firmness of the RGD peptides with the cells (ex: MDAMB21) and their rupture using external heat stimulation. 1 Since in vivo conditions in tumors normally produce a higher temperature than the surrounding areas, and also that it has been proved that the physical force generated from the expansion of the cells when they were heated was sufficient to kill them, that type of thermally responsive hydrogels proved to be highly advantageous options for achieving targeted cell killing [28].…”