Programmable Peptides Activated Macropinocytosis for Direct Cytosolic Delivery

• DOI: 10.1002/adhm.202301162
• Publication Date: 2023-07-14T14:20:53Z
• Authors: Yan‐Lei Fan; Ni‐Yuan Zhang; Da‐Yong Hou; Yi Hao; Rui Zheng; Jia Yang; Zhi Fan; Hong‐Wei An; Hao Wang
• Keywords: Pinocytosis

Abstract Bioactive macromolecules show great promise for the treatment of various diseases. However, cytosolic delivery peptide‐based drugs remains a challenging task owing to existence multiple intracellular barriers and ineffective endosomal escape. To address these issues, herein, programmable self‐assembling peptide vectors are reported amplify cargo internalization into cytoplasm through receptor‐activated macropinocytosis. Programmable vector‐active human epidermal growth factor receptor‐2 (HER2) signaling induces macropinocytosis pathway, achieving efficient uptake in tumor cells. Shrinking macropinosomes accelerate process assembly dynamics form nanostructures increase accumulation retention. Inductively coupled plasma mass (ICP‐MS) spectrometry quantitative analysis indicates that Gd efficiency tissue pathway is improved 2.5‐fold compared with use active targeting molecular delivery. Finally, nanoparticles delivery, bioactive self‐assembly maintains high drug activity (the IC 50 decreased twofold) achieves effective inhibition cell growth. represent promising platform diverse drugs, including peptides, biologics.