A foe-inspired friend: Constructing a tumor tissue-mimicking biomaterial to study intratumoral drug transport

Abstract

The design of an in vitro model of the tumor microenvironment and its implementation on drug screening of new anticancer therapies is an active challenge that sits at the interface of biomaterials and cancer biology. As recent clinical successes of human intratumoral therapies stimulate research on intratumoral delivery, a need for an in vitro 3D tumor model to screen intratumoral therapies arises. Since the drug formulation is injected directly into the tumor, the biophysics of the tumor microenvironment affecting intratumoral retention must be considered in the design of a tumor model. Fibrotic regions characteristic of solid tumors typically are rich in collagen I fibers. Using shear rheology, tumors with lower collagen density were shown to have a lower stiffness. Similarly, the stiffness of the hyaluronic acid hydrogel models was increased with the addition of collagen fibers to model the bulk biomechanical properties of solid tumors. Hyaluronic acid-based hydrogels were then used as intratumoral injection site simulators to model in vitro the retention of glatiramer acetate (GA) and polyethylene glycol (PEG) administered intratumorally. Both compounds were also injected in murine head & neck tumors and their retention was studied ex vivo for comparison. Retention of GA in the hydrogels was significantly longer than PEG as expected, which was confirmed in the solid tumors. Finally, the biocompatibility of the designed models was assessed by 3D culturing human head & neck cancer cells. Cancer cell viability in the scaffolds was demonstrated, thus setting ground for future applications to assess intratumoral retention time and bulk biomechanical characteristics of solid tumors.