Li, Yuexuan2023-03-272023-03-272023-01https://hdl.handle.net/11299/253416University of Minnesota Ph.D. dissertation. January 2023. Major: Pharmaceutics. Advisor: Hongbo Pang. 1 computer file (PDF); xiv, 161 pages.Peptides are emerging as a useful tool in assisting the delivery of nanomaterial and other macromolecules into cells and tissues. Covalent coupling has been the mainstream strategy in such applications. Despite the high efficiency, it requires additional chemical modifications of nanomaterials, which is undesirable for clinical translation. The “bystander” effect presents a method to bypass the covalent coupling and facilitate the cell entry of nanomaterials and macromolecules through simply co-administration with cell-penetrating peptides (CPPs). While only a few cationic CPPs were previously reported to induce the bystander effect, this dissertation has investigated an array of CPPs and discovered that Transportan (TP) peptide, an amphiphilic CPP, is among the best CPPs to stimulate the cellular uptake of nanoparticles (NPs) in the bystander manner. Interestingly, bystander activities vary among bystander NPs with different physical properties. Varying the sizes of NPs, we have found that 50 nm is the optimal diameter for bystander uptake. Together, these studies will open new perspectives for peptide applications in nanomaterial delivery and provide insights into the future design of nanostructures for intracellular delivery.enThesis or Dissertation