Stiffness-optimized drug-loaded matrix for selective capture and elimination of cancer cells

The controlled release and targeting of anticancer drugs to cancer tissues are important issues for reducing adverse side effects of these drugs and improving their therapeutic efficacy. However, the passive release and unsatisfied selectivity of drug carriers are liable to cause toxicity toward normal cells. To overcome this problem, we focused on the intrinsic motility of cancer cells in response to a specific extracellular micro-mechanical environment. In this study, we developed an anticancer-drug-loaded hydrogel matrix with optimized stiffness to selectively capture and eliminate only cancer cells. This matrix was fabricated with photocurable gelatin by electrospinning, photo-crosslinking and finally swelling, which produced chemically-crosslinked microfiber gels and enough void space between the gel fibers inside the matrix. The stiffness of the matrix was regulated by photo-crosslinking conditions and adjusted so as to induce invasion by cancer cells, but not normal cells, to reduce unnecessary toxicity. Tumorigenic MDA-MB-231 cells tended to invade the stiffness-optimized matrix with fiber elasticity lower than 20 kPa, while the invasion of nontumorigenic MCF-10A cells was inhibited under the same conditions, regardless of whether or not the matrix was loaded with the model drug docetaxel. Limited passive diffusion of the drug was confirmed in vitro, and the anticancer/toxicity of the matrix was investigated through live/dead staining and CCK-8 assays. The stiffness-optimized docetaxel-loaded matrix was found to have a selective killing effect only on invaded cancer cells, suggesting the potential effectiveness of such a cancer-capturing/eliminating matrix.