Tumor Presence Induces Global Immune Changes and Enhances Nanoparticle Clearance

ACS Nano. 2016 Jan 26;10(1):861-70. doi: 10.1021/acsnano.5b05999. Epub 2015 Dec 2.

Abstract

Long-circulating nanoparticles are essential for increasing tumor accumulation to provide therapeutic efficacy. While it is known that tumor presence can alter the immune system, very few studies have explored this impact on nanoparticle circulation. In this report, we demonstrate how the presence of a tumor can change the local and global immune system, which dramatically increases particle clearance. We found that tumor presence significantly increased clearance of PRINT hydrogel nanoparticles from the circulation, resulting in increased accumulation in the liver and spleen, due to an increase in M2-like macrophages. Our findings highlight the need to better understand interactions between immune status and nanoparticle clearance, and suggest that further consideration of immune function is required for success in preclinical and clinical nanoparticle studies.

Keywords: immunology; intravital; nanoparticle; orthotopic; pharmacokinetic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / pharmacology
  • Cisplatin / chemistry
  • Cisplatin / pharmacokinetics*
  • Cisplatin / pharmacology
  • Drug Compounding
  • Ear / anatomy & histology
  • Ear / blood supply
  • Humans
  • Hydrogels / chemistry
  • Immunity, Innate
  • Liver / drug effects
  • Liver / immunology
  • Liver / metabolism
  • Lung / drug effects
  • Lung / immunology*
  • Lung / pathology
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Nanoparticles / chemistry
  • Nanoparticles / metabolism*
  • Neoplasm Transplantation
  • Primary Cell Culture
  • Spleen / drug effects
  • Spleen / metabolism
  • Time-Lapse Imaging

Substances

  • Antineoplastic Agents
  • Hydrogels
  • Cisplatin