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

• A 3D bioprinted model able to mimic CRC, for new nanomedicine test in cancer therapy. • Novel bioink ensures controlled, reproducible hollow conduits for cells co-culture • 3D model as an in vitro twin, bridging preclinical in vitro to in vivo cancer research. • Hybrid NPs target CRC in 3D volume, sparing healthy cells, reinforcing model versatility. • Stimuli-responsive NPs tested in CRC model, supporting research for effective treatments. 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.