Enhancing therapeutic efficacy through designed aggregation of nanoparticles

Tanmoy Sadhukha, Timothy S. Wiedmann, Jayanth Panyam

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Particle size is a key determinant of biological performance of sub-micron size delivery systems. Previous studies investigating the effect of particle size have primarily focused on well-dispersed nanoparticles. However, inorganic nanoparticles are prone to aggregation in biological environments. In our studies, we examined the consequence of aggregation on superparamagnetic iron oxide (SPIO) nanoparticle-induced magnetic hyperthermia. Here we show that the extent and mechanism of hyperthermia-induced cell kill is highly dependent on the aggregation state of SPIO nanoparticles. Well-dispersed nanoparticles induced apoptosis, similar to that observed with conventional hyperthermia. Sub-micron size aggregates, on the other hand, induced temperature-dependent autophagy through generation of oxidative stress. Micron size aggregates caused rapid membrane damage, resulting in acute cell kill. Overall, this work highlights the potential for developing highly effective anticancer therapeutics through designed aggregation of nano delivery systems.

Original languageEnglish (US)
Pages (from-to)7860-7869
Number of pages10
JournalBiomaterials
Volume35
Issue number27
DOIs
StatePublished - Sep 2014

Bibliographical note

Funding Information:
We thank the Flow Cytometry Core Facility of the Masonic Cancer Center, a comprehensive cancer center designated by the National Cancer Institute, supported in part by P30 CA77598. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. We also thank the Comparative Pathology core facility for the preparation of H & E and Prussian blue stained slides.

Funding Information:
Funding support from the Department of Defense ( CA093453 ).

Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.

Keywords

  • Aggregation
  • Apoptosis
  • Autophagy
  • Magnetic hyperthermia
  • Necrosis
  • Superparamagnetic iron oxide

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