3D bioprinted colorectal co-culture model to explore nanoparticles targeting and stimuli responsive treatments against cancer

Colorectal cancer (CRC) is a major global health challenge and a leading cause of cancer-related deaths, with prevalence expected to double by 2040. Traditional treatments face significant limitations, including resistance, recurrence, and toxicity. Nanomedicine offers promising alternatives through advanced nanoparticles, such as drug-delivering or stimulus-activated systems, but clinical translation remains challenging. Current animal models often fail to accurately predict human outcomes, highlighting the need for better testing platforms. Three-dimensional (3D) colorectal cancer models provide an ethical, cost-effective alternative to animal studies, mimicking human tumor microenvironments with high fidelity. Here we bioprinted 3D hollow conduits to develop a CRC model, co-culturing healthy and cancer cells, enabling controlled and rapid testing of therapies with improved reproducibility. Unlike 2D cultures or animal models, the proposed 3D bioprinted model provides insights into tumor-specific responses under therapeutic treatments and bio-stability over long time span. It serves as in vitro biological twin of CRC to test innovative nanomedicine treatments, aiming to bridge preclinical and clinical research. We create hybrid biomimetic nanoparticles designed to target CRC tumors while sparing healthy tissue. These nanoparticles are activated by acoustic waves to induce cancer-specific cell death. Their safety and efficacy are tested in the bioprinted 3D models, advancing personalized CRC treatments.