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

Wei Lu1, Chiyi Xiong, Rui Zhang

  • 1Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Insights

Targeting ligand type influences nanoparticle delivery in tumors. Agonist-conjugated nanoparticles actively transport into tumors, enhancing uptake via receptor-mediated endocytosis and transcytosis.

Area of Science:

  • Nanomedicine
  • Cancer Theranostics
  • Tumor Biology

Background:

  • Targeted nanoparticles are crucial for cancer theranostics.
  • Extravascular transport of nanoparticles in tumors is not fully understood.
  • Targeting ligands may influence nanoparticle distribution within tumors.

Purpose of the Study:

  • To investigate how targeting ligand type (agonist vs. antagonist) affects nanoparticle extravascular transport and tumor uptake.
  • To elucidate the mechanism of nanoparticle transport across tumor tissues.

Main Methods:

  • Utilized B16/F10 melanoma cells expressing melanocortin type-1 receptor (MC1R).
  • Conjugated MC1R agonist or antagonist ligands to pegylated hollow gold nanospheres (HAuNS).
  • Employed multilayer tumor cell models and transmission electron microscopy to study nanoparticle transport.

Main Results:

  • MC1R agonist-conjugated HAuNS were internalized via receptor-mediated endocytosis and transcytosis.
  • MC1R antagonist-conjugated HAuNS remained cell-surface bound.
  • Agonist-conjugated nanoparticles showed significantly higher tumor uptake than non-targeted HAuNS.

Conclusions:

  • The nature of targeting ligands actively directs nanoparticle uptake and intratumoral distribution.
  • Receptor-mediated endocytosis and transcytosis facilitate nanoparticle transport, overcoming biological barriers in solid tumors.
  • This active transport mechanism enhances nanoparticle delivery for cancer theranostics.

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