Development of Clay-Based Multifunctional Nanomedicine Loaded with the C-Terminal Domain Trun2 of rhCNB for Targeted Colon Cancer Treatment

Abstract Recombinant human calcineurin B subunit (rhCNB) has emerged as a promising antitumour therapeutic candidate. Extensive research has shown that the C-terminal region (residues 85–169) of rhCNB, termed Trun2 in this study, serves as the key functional domain responsible for both its antitumour activity and tumour-targeting ability. Targeted drug delivery is a promising strategy for enhancing treatment efficacy while reducing the systemic toxicity and multidrug resistance associated with conventional chemotherapy. In this article, we developed multifunctional layered double hydroxide (LDH) nanoparticles coloaded with Trun2 and paclitaxel (PTX) or doxorubicin (DOX) for the targeted treatment of colon cancer. LDH-PTX-Trun2 or LDH-DOX-Trun2 nanoparticles effectively suppressed colon cancer cell proliferation both in vitro and in vivo. Furthermore, these nanoparticles promoted the secretion and production of antitumour cytokines by bone marrow-derived dendritic cells (BMDCs) and improved tumour site-specific drug delivery. These findings indicated that Trun2 is a promising tumour-targeting small molecular protein for nanoparticle-based drug delivery systems, offering a strategic approach to improving therapeutic precision and efficacy.