Multifunctional hollow gold nanoparticles designed for triple combination therapy and CT imaging

J Control Release. 2015 Jun 10:207:77-85. doi: 10.1016/j.jconrel.2015.04.007. Epub 2015 Apr 8.

Abstract

Hollow gold nanoparticles (HGNP) are a novel class of hybrid metal nanoparticles whose unique optical and morphological properties have spawned new applications including more effective cancer therapy. The shell thickness of HGNPs can tune the surface plasmon resonance to the near infrared light, resulting in photothermal ablation of tumors with optimal light penetration in tissue. The hollow cavity within a HGNP is able to accommodate a high payload of chemotherapeutic agents. They have also been used for enhancing radiosensitization in tumors during radiotherapy due to the high X-ray absorption capability of gold particles. However, no report has yet been published that utilize HGNPs for the triple combination therapy and CT imaging. In this study, we synthesized HGNPs which exhibit better response to radiation for therapy and imaging and demonstrated the effects of combined chemotherapy, thermal and radiotherapy. This combination strategy presented delayed tumor growth by 4.3-fold and reduced tumor's weight by 6.8-fold compared to control tumors. In addition, we demonstrated the feasibility of HGNP as a CT imaging agent. It is expected that translating these capabilities to human cancer patients could dramatically increase the antitumor effect and potentially overcome resistance to chemotherapeutic agents and radiation.

Keywords: Chemotherapy; Gold nanoparticles; Hyperthermia; Radiosensitization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / chemistry
  • Apoptosis
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical
  • Chemoradiotherapy / methods*
  • Contrast Media / administration & dosage*
  • Contrast Media / chemistry
  • DNA Breaks, Double-Stranded
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Drug Carriers*
  • Gold / administration & dosage*
  • Gold / chemistry
  • Histones / metabolism
  • Kinetics
  • Laser Therapy / methods*
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Male
  • Metal Nanoparticles*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Predictive Value of Tests
  • Radiation Tolerance
  • Solubility
  • Technology, Pharmaceutical / methods
  • Time Factors
  • Tumor Burden
  • X-Ray Microtomography / methods*
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • Contrast Media
  • Drug Carriers
  • H2AX protein, human
  • Histones
  • Gold
  • Doxorubicin