Rational Design of Dual-Targeted Nanomedicines for Enhanced Vascular Permeability in Low-Permeability Tumors

with tunable ratios of RGD-targeting and intrinsic TfR1-targeting ligands. These Dt-FTn constructs were employed to investigate the interaction between receptor-mediated vascular permeability and dual-targeted nanomedicines in low-permeability tumors. Through machine learning-based single vessel analysis, we uncovered the crucial role of dual-receptor expression profiles in determining the vascular transport of dual-targeted nanomedicines in tumors with low permeability. Using a patient-derived colon cancer model, we demonstrated a proof-of-concept that the optimal proportions of dual ligands in these nanomedicines can be customized based on tumor cell receptor expression profiles. This study provides valuable insights and guiding principles for the rational design of dual-targeted nanomedicines for tumor-targeted delivery.