Sub-100nm gold nanomatryoshkas improve photo-thermal therapy efficacy in large and highly aggressive triple negative breast tumors

J Control Release. 2014 Oct 10;191:90-97. doi: 10.1016/j.jconrel.2014.07.038. Epub 2014 Jul 19.

Abstract

There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or necrotic regions. We report the performance advantages obtained by sub 100nm gold nanomatryushkas, comprising concentric gold-silica-gold layers compared to conventional ~150nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000mm(3)) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5× accumulation within large tumors results in superior therapy efficacy.

Keywords: Gold nanoparticle; Multilayer nanoshells Au/SiO(2)/Au; Nanomatryoshka; Near infrared; Photothermal therapy.

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
  • Cell Line, Tumor
  • Female
  • Gold / administration & dosage*
  • Gold / chemistry
  • Humans
  • Hyperthermia, Induced / instrumentation
  • Hyperthermia, Induced / methods*
  • Injections, Intravenous
  • Lasers, Semiconductor
  • Mice
  • Mice, Nude
  • Nanomedicine / methods
  • Nanoshells*
  • Particle Size
  • Phototherapy / instrumentation
  • Phototherapy / methods*
  • Polyethylene Glycols / chemistry
  • Silicon Dioxide / chemistry
  • Surface Properties
  • Time Factors
  • Transducers
  • Triple Negative Breast Neoplasms / pathology
  • Triple Negative Breast Neoplasms / therapy*
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Polyethylene Glycols
  • Gold
  • Silicon Dioxide