Melanin-Inspired Nanoparticle Tattoo Inks for Precise Marking and Surveillance of Gastrointestinal Lesions

Abstract Accurate endoscopic marking of suspicious lesions and polyps is essential for the effective surgical management of gastrointestinal (GI) diseases, including colorectal cancer and inflammatory bowel disease. Currently, lesion localization relies on submucosal injection of a carbon-based tattoo ink; however, this ink exhibits extensive tissue diffusion and extravasation, leading to poor spatial fidelity, compromised precision, and risk for fibrotic responses. Given the need for contrast relative to endoscopic white light and biocompatibility, we report here the design and evaluation of melanin-inspired nanoparticle tattoo (MINT) inks, formulated from synthetic melanin nanoparticles and biopolymer-encapsulated synthetic melanin. MINT inks are designed to be durable, high-contrast, easily injectable, and colloidally stable for at least 2 months and to elicit minimal macrophage-mediated inflammatory responses in vitro. In live porcine colon studies, submucosal injection of MINT inks resulted in highly localized tattoos with minimal lateral spread over 9 weeks of follow-up, which is a significant advantage over the extensive diffusion observed with clinical carbon ink. MINT tattoo markings were distinctly visible from both mucosal and serosal surfaces of the intestine and enabled reproducible multipoint and quadrant-based marking, which enhanced spatial orientation. Collectively, these findings demonstrate that MINT inks are biocompatible and capable of providing precise, long-lasting, high-contrast marking of lesions in the colon. By overcoming the limitations of conventional carbon-particle-based tattoos, MINT inks represent a promising next-generation contrast agent for improving endoscopic localization and surgical outcomes in GI diseases.