Receptor-mediated transcytosis: A mechanism for active extravascular transport of nanoparticles in solid tumors

Wei Lu, Chiyi Xiong, Rui Zhang, Lifang Shi, Miao Huang, Guodong Zhang, Shaoli Song, Qian Huang, Gang Yu Liu, Chun Li

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


Targeted nanoparticle-based delivery systems have been used extensively to develop effective cancer theranostics. However, how targeting ligands affect extravascular transport of nanoparticles in solid tumors remains unclear. Here, we show, using B16/F10 melanoma cells expressing melanocortin type-1 receptor (MC1R), that the nature of targeting ligands, i.e., whether they are agonists or antagonists, directs tumor uptake and intratumoral distribution after extravasation of nanoparticles from tumor vessels into the extravascular fluid space. Pegylated hollow gold nanospheres (HAuNS, diameter = 40 nm) coated with MC1R agonist are internalized upon ligand-receptor binding, whereas MC1R antagonist-conjugated HAuNS remain attached on the cell surface. Transcellular transport of agonist-conjugated HAuNS was confirmed by a multilayer tumor cell model and by transmission electron microscopy. MC1R agonist- but not MC1R antagonist-conjugated nanoparticles exhibit significantly higher tumor uptake than nontargeted HAuNS and are quickly dispersed from tumor vessels via receptor-mediated endocytosis and subsequent transcytosis. These results confirm an active transport mechanism that can be used to overcome one of the major biological barriers for efficient nanoparticle delivery to solid tumors.

Original languageEnglish (US)
Pages (from-to)959-966
Number of pages8
JournalJournal of Controlled Release
Issue number3
StatePublished - Aug 10 2012


  • Agonists
  • Antagonists
  • Melanocortin type-1 receptor (MC1R)
  • Nanoparticles
  • Transcytosis

ASJC Scopus subject areas

  • Pharmaceutical Science


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