Enhancing nanoparticle accumulation and retention in desmoplastic tumors via vascular disruption for internal radiation therapy

Andrew B. Satterlee, Juan D. Rojas, Paul A. Dayton, Leaf Huang

Research output: Research - peer-reviewArticle

  • 6 Citations

Abstract

Aggressive, desmoplastic tumors are notoriously difficult to treat because of their extensive stroma, high interstitial pressure, and resistant tumor microenvironment. We have developed a combination therapy that can significantly slow the growth of large, stroma-rich tumors by causing massive apoptosis in the tumor center while simultaneously increasing nanoparticle uptake through a treatment-induced increase in the accumulation and retention of nanoparticles in the tumor. The vascular disrupting agent Combretastatin A-4 Phosphate (CA4P) is able to increase the accumulation of radiation-containing nanoparticles for internal radiation therapy, and the retention of these delivered radioisotopes is maintained over several days. We use ultrasound to measure the effect of CA4P in live tumor-bearing mice, and we encapsulate the radio-theranostic isotope 177Lutetium as a therapeutic agent as well as a means to measure nanoparticle accumulation and retention in the tumor. This combination therapy induces prolonged apoptosis in the tumor, decreasing both the fibroblast and total cell density and allowing further tumor growth inhibition using a cisplatin-containing nanoparticle.

LanguageEnglish (US)
Pages253-269
Number of pages17
JournalTheranostics
Volume7
Issue number2
DOIs
StatePublished - 2017

Fingerprint

Nanoparticles
Blood Vessels
Radiotherapy
Neoplasms
Therapeutics
Phosphates
Apoptosis
Growth
fosbretabulin
Lutetium
Tumor Microenvironment
Radio
Radioisotopes
Isotopes
Cisplatin
Fibroblasts
Cell Count
Radiation
Pressure
Theranostic Nanomedicine

Keywords

  • CA4P
  • Cancer
  • Cisplatin
  • Desmoplastic
  • EPR
  • Nanoparticle
  • Theranostic

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

Enhancing nanoparticle accumulation and retention in desmoplastic tumors via vascular disruption for internal radiation therapy. / Satterlee, Andrew B.; Rojas, Juan D.; Dayton, Paul A.; Huang, Leaf.

In: Theranostics, Vol. 7, No. 2, 2017, p. 253-269.

Research output: Research - peer-reviewArticle

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