Macropinocytosis as a cell entry route for peptide-functionalized and bystander nanoparticles

Yue Xuan Li, Hong Bo Pang

Research output: Contribution to journalReview articlepeer-review


Endocytic pathways provide the primary route for therapeutic and diagnostic nanoparticles (NPs) to enter cells and subcellular compartments. A better understanding of these cell entry processes will not only aid in nanomaterial applications but also broaden our knowledge of cell biology. Among the endocytic routes, macropinocytosis has unique characteristics for engulfing NPs and other large cargo, yet its molecular machinery and involvement in NP uptake are far less characterized relative to other pathways. In this review, we summarize the current knowledge on the macropinocytic machinery, and its involvement in NP internalization. Particularly, we differentiate ligand (specifically peptide)-functionalized and unfunctionalized NPs (bystander NPs). While most of previous research focused on ligand-functionalized NPs, we showcase here a synergistic effect between these two NP types during their cell entry through receptor-mediated macropinocytosis. The regulation of NP uptake efficiency by extracellular amino acids is also highlighted in the context of interconnections between macropinocytosis and metabolic signaling. These discussions may fuel future research interests in improving NP internalization through this pathway, and open a new avenue to study the interplay among endocytosis, metabolism and nanomedicine.

Original languageEnglish (US)
Pages (from-to)1222-1230
Number of pages9
JournalJournal of Controlled Release
StatePublished - Jan 10 2021

Bibliographical note

Funding Information:
The authors acknowledge the funding support from the National Institute of Health ( R01CA214550 , R01GM133885 and R21EB022652 ) and the State of Minnesota ( MNP #19.08 ).

Publisher Copyright:
© 2020 Elsevier B.V.

PubMed: MeSH publication types

  • Journal Article
  • Review

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