Therapeutic and scintigraphic applications of polymeric micelles: combination of chemotherapy and radiotherapy in hepatocellular carcinoma

Int J Nanomedicine. 2015 Dec 16:10:7443-54. doi: 10.2147/IJN.S91008. eCollection 2015.

Abstract

This study evaluated a multifunctional micelle simultaneously loaded with doxorubicin (Dox) and labeled with radionuclide rhenium-188 ((188)Re) as a combined radiotherapy and chemotherapy treatment for hepatocellular carcinoma. We investigated the single photon emission computed tomography, biodistribution, antitumor efficacy, and pathology of (188)Re-Dox micelles in a murine orthotopic luciferase-transfected BNL tumor cells hepatocellular carcinoma model. The single photon emission computed tomography and computed tomography images showed high radioactivity in the liver and tumor, which was in agreement with the biodistribution measured by γ-counting. In vivo bioluminescence images showed the smallest size tumor (P<0.05) in mice treated with the combined micelles throughout the experimental period. In addition, the combined (188)Re-Dox micelles group had significantly longer survival compared with the control, (188)ReO4 alone (P<0.005), and Dox micelles alone (P<0.01) groups. Pathohistological analysis revealed that tumors treated with (188)Re-Dox micelles had more necrotic features and decreased cell proliferation. Therefore, (188)Re-Dox micelles may enable combined radiotherapy and chemotherapy to maximize the effectiveness of treatment for hepatocellular carcinoma.

Keywords: 188Re-Dox micelles; chemotherapeutic; hepatocellular carcinoma; radiotherapeutic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / therapeutic use
  • Carcinoma, Hepatocellular / diagnostic imaging
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Combined Modality Therapy
  • Doxorubicin / therapeutic use*
  • Drug Delivery Systems*
  • Female
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Micelles
  • Polymers / chemistry*
  • Radiopharmaceuticals / administration & dosage
  • Radiopharmaceuticals / pharmacokinetics
  • Rhenium / administration & dosage*
  • Rhenium / pharmacokinetics
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • Micelles
  • Polymers
  • Radiopharmaceuticals
  • Rhenium
  • Doxorubicin