Depolymerization of hyaluronan using PEGylated human recombinant hyaluronidase promotes nanoparticle tumor penetration

Daniel H.S. Brundel, Orlagh M. Feeney, Cameron J. Nowell, Estelle J.A. Suys, Gracia Gracia, Lisa M. Kaminskas, Michelle M. McIntosh, David W. Kang, Christopher J.H. Porter

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Aim: Delivery of nanoparticles (NPs) to tumors can be impeded by high levels of hyaluronan (HA) in the stroma. Enzymatic depolymerization of HA with PEGylated hyaluronidase (PEGPH20) improves the delivery of antibodies to tumors. However, it is unknown whether NP delivery is enhanced by this strategy. 

Methods: The impact of PEGPH20 pretreatment on the uptake and tumor penetration of model PEGylated polystyrene NPs was studied in mice with orthotopic breast cancers. 

Results: Tumor oxygenation and NP penetration, but not overall tumor uptake, of 50 nm NPs, was significantly enhanced by PEGPH20 pre-administration. 

Conclusion: PEGPH20 has the potential to improve intratumoral penetration of NP-based drug delivery systems and enhance access to cancer cells in poorly vascularized regions of the tumor.

Original languageEnglish
Pages (from-to)275-292
Number of pages18
JournalNanomedicine
Volume16
Issue number4
DOIs
Publication statusPublished - 9 Feb 2021

Keywords

  • hyaluronan
  • hyaluronidase
  • intratumoral penetration
  • polystyrene nanoparticle
  • tumor stroma

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