Co-administration of Transportan Peptide Enhances the Cellular Entry of Liposomes in the Bystander Manner Both in Vitro and in Vivo

Yuexuan Li, Nianwu Wang, M. Mahadi Hasan, Hong Bo Pang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Liposomes have been widely used as a drug delivery vector. One way to further improve its therapeutic efficacy is to increase the cell entry efficiency. Covalent conjugation with cell-penetrating peptides (CPPs) and other types of ligands has been the mainstream strategy to tackle this issue. Although efficient, it requires additional chemical modifications on liposomes, which is undesirable for clinical translation. Our previous study showed that the transportan (TP) peptide, an amphiphilic CPP, was able to increase the cellular uptake of co-administered, but not covalently coupled, metallic nanoparticles (NPs). Termed bystander uptake, this process represents a simpler method to increase the cell entry of NPs without chemical modifications. Here, we extended our efforts to liposomes. Our results showed that co-administration with the TP peptide improved the internalization of liposome into a variety of cell lines in vitro. This effect was also observed in primary cells, ex vivo tumor slices, and in vivo tumor tissues. On the other hand, this peptide-assisted liposome internalization did not apply to cationic CPPs, which were the main inducers for bystander uptake in previous studies. We also found that TP-assisted bystander uptake of liposome is receptor dependent, and its activity is more sensitive to the inhibitors of the macropinocytosis pathway, underlining the potential cell entry mechanism. Overall, our study provides a simple strategy based on TP co-administration to increase the cell entry of liposomes, which may open up new avenues to apply TP peptides in nanotherapeutics.

Original languageEnglish (US)
Pages (from-to)4123-4134
Number of pages12
JournalMolecular pharmaceutics
Issue number11
StatePublished - Nov 7 2022

Bibliographical note

Funding Information:
This study was supported by the National Institute of Health (R01CA214550 and R01GM133885) and the State of Minnesota (MNP #19.08).

Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.


  • bystander uptake
  • liposome
  • transportan

PubMed: MeSH publication types

  • Journal Article
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural


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