Multipronged nano-based approach targeting rectal cancer and radiation fibrosis

Diogo Coelho – PhD Student, i3S - Instituto de Investigação e Inovação em Saúde, Universidade Do Porto, Porto, Portugal; Eduarda Silva – Assistant Professor, Associate Laboratory i4HB - Institute for Health and Bioeconomy, University Institute of Health Sciences - CESPU, 4585-116 Gandra, Portugal; UCIBIO - Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal; Maria Oliveira – Group leader/ Principal Investigator, i3S - Instituto de Investigação e Inovação em Saúde, Universidade Do Porto, Porto, Portugal; Bruno Sarmento – Group leader/ Principal Investigator, i3S - Instituto de Investigação e Inovação em Saúde, Universidade Do Porto, Porto, Portugal

Introduction: Colorectal cancer (CRC) represents around 10% of all cancer cases worldwide, with rectal cancer (RC) comprising over one third and showing a concerning rise incidence among young adults ¹. Standard RC treatment combines radiotherapy with 5‑fluorouracil (5‑FU), but its systemic administration lacks tumor selectivity, while radiation‑induced fibrosis not only reduces patients’ quality of life but also hampers immune cell infiltration after treatment ². To address these limitations, we propose a triple-modal strategy combining a carcinoembryonic antigen (CEA)-targeted solid lipid nanoparticle (SLN) encapsulating 5-FU, galunisertib (TGF‑β receptor I kinase inhibitor), and radiotherapy.