Multiporous PMMA microballs as a novel fluorescence tissue marker

Abstract

Identification of target tissues such as tumors is essential to minimize unnecessary resection of normal tissues during surgery. However, conventional tissue markers using metal clips, ink tattooing, and metal-coil embedded pellets are not appropriate for the real-time detection of tumor sites during laparoscopic surgery or long-term follow-up of target tissues without ionizing irradiation. Therefore, the development of safe and novel tissue markers is urgently required for clinical practice. In this study, we developed a near-infrared (NIR) fluorescence marker (MicBall) to achieve precise and accurate marking for laparoscopic surgery, along with long-term marking capability. MicBall generated bright NIR fluorescence comparable to that of an indocyanine green-human serum albumin solution. MicBall is suitable for evading phagocytosis by macrophages, thereby allowing long-term preservation at the injection sites. Furthermore, the introduction of multiple, small-sized, and separate pore structures inside MicBall provided long-term labeling capabilities by preventing unwanted NIR dye release. The morphology, size, and NIR fluorescence of MicBall did not change after γ-ray irradiation for sterilization. Results from in vivo evaluation of MicBall/alginate hydrogels corroborated their potential utility as tissue markers for real-time detection of target sites, as well as for long-term follow-up and subsequent imaging-guided resection of marking sites.