Аннотация:Modular nanotransporters (MNTs) are drug delivery systems for targeted cancer treatment.As MNTs are composed of several modules, they offer the advantage of high specificity andbiocompatibility in delivering drugs to the target compartment of cancer cells. The large carriermodule brings together functioning MNT modules and serves as a platform for drug attachment. Thedevelopment of smaller-sized MNTs via truncation of the carrier module appears advantageous in facilitatingtissue penetration. In this study, two new MNTs with a truncated carrier module containingeither an N-terminal (MNTN) or a C-terminal (MNTC) part were developed by genetic engineering.Both new MNTs demonstrated a high affinity for target receptors, as revealed by fluorescent-labeled ligand-competitive binding. The liposome leakage assay proved the endosomolytic activity of MNTs. Binding to the importin heterodimer of each truncated MNT was revealed by a thermophoresisassay, while only MNTN possessed binding to Keap1. Finally, the photodynamic efficacy of thephotosensitizer attached to MNTN was significantly higher than when attached to either MNTC orthe original MNTs. Thus, this work reveals that MNT’s carrier module can be truncated withoutlosing MNT functionality, favoring the N-terminal part of the carrier module due to its ability tobind Keap1.