Fluidity of biodegradable substrate regulates carcinoma cell behavior: A novel approach to cancer therapy

Abstract

Although various polymeric substrates with different stiffness have been applied for the regulation of cells’ fate, little attention has been given to the effects of substrates’ fluidity. Here, we implement for the first time biodegradable polymer with fluidic property for cancer therapy by investigating cell adhesion, proliferation, apoptosis/death, cycles of cancer cells as well as the anticancer drug efficacy. To achieve this, we prepared crosslinked and non-crosslinked copolymers of ɛ-caprolactone-<em>co</em>-D, L-lactide (P(CL-<em>co</em>-DLLA)). The tensile test showed the crosslinked P(CL-<em>co</em>-DLLA) substrate has the stiffness of 261 kPa while the loss modulus <em>G’’</em> of the non-crosslinked substrate is always higher than the storage modulus <em>G’</em> (<em>G’’</em>/<em>G’</em>=3.06), indicating a quasi-liquid state. Human lung epithelial adenocarcinoma cells on crosslinked substrate showed well- spread actin stress fibers and visible focal adhesion with an increased S phase (decreased G0/G1 phase). The cells on non-crosslinked substrate, on the other hand, showed rounded morphology without visible focal adhesion and an accumulated G0/G1 phase (decreased S phase). These results suggest that the behavior of cancer cells not only depends on stiffness but also the fluidity of P(CL-<em>co</em>-DLLA) substrate. In addition, the effects of substrate’s fluidity on anti-cancer drug efficacy were also investigated. The IC₅₀ values of paclitaxel for cancer cells on crosslinked and non-crosslinked substrates are 5.46 and 2.86 nM, respectively. These results clearly indicate that the fluidity of polymeric materials should be considered as one of the crucial factors to study cellular functions and molecular mechanism of cancer progression.