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Junction opener protein increases nanoparticle accumulation in solid tumors

Christine E Wang1, Roma C Yumul2, Jonathan Lin3

  • 1Department of Bioengineering and Molecular Engineering and Sciences Institute, University of Washington, 3720 15th Ave NE, Seattle, WA 98195, United States.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|January 7, 2018
PubMed

Insights

The junction opener (JO) protein enhances anticancer drug delivery by increasing nanoparticle accumulation in tumors. JO protein significantly boosts the accumulation of smaller gold nanoparticles (35nm) but not larger ones (120nm) in tumors.

Area of Science:

  • Oncology
  • Nanomedicine
  • Biotechnology

Background:

  • Carcinomas possess tight junctions that impede anticancer agent penetration, limiting therapeutic effectiveness, particularly for nano-carrier systems.
  • The virus-derived junction opener (JO) protein transiently opens intercellular junctions in epithelial tumors by cleaving desmoglein-2 (DSG2).
  • Previous studies demonstrated JO protein's ability to enhance the efficacy of various anticancer agents in murine models by improving intratumoral drug penetration.

Purpose of the Study:

  • To investigate the size-dependent impact of the junction opener (JO) protein on nanocarrier biodistribution.
  • To evaluate the effect of JO protein on the tumor accumulation and intratumoral penetration of gold nanoparticles (AuNPs) of different sizes.

Main Methods:

  • Utilized PEGylated gold nanoparticles (AuNPs) of two distinct sizes (35nm and 120nm) as model nanocarriers.
  • Administered JO protein and AuNPs to murine tumor models of varying sizes (medium and large).
  • Quantified AuNP biodistribution and tumor accumulation using inductively coupled plasma mass spectrometry (ICP-MS) and analyzed intratumoral distribution via image analysis of tumor sections.

Main Results:

  • JO protein significantly increased the bulk tumor accumulation of 35nm AuNPs but not 120nm AuNPs in both medium and large tumors.
  • Image analysis confirmed JO-mediated enhancement of AuNP tumor accumulation.
  • Intratumoral distribution analysis revealed that most AuNPs remained within 100μm of vasculature, with no significant JO-mediated effect on penetration profiles at 6 hours.

Conclusions:

  • The junction opener (JO) protein demonstrates a size-dependent effect on nanocarrier tumor accumulation, favoring smaller nanoparticles.
  • JO protein can enhance the delivery of specific-sized nanocarriers into tumors, potentially improving therapeutic outcomes.
  • Further research is warranted to optimize nanocarrier size for JO-mediated drug delivery strategies.
Keywords:
Gold nanoparticlesImage analysisJunction openingTumor penetration

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