PH-controlled gas-generating mineralized nanoparticles: A theranostic agent for ultrasound imaging and therapy of cancers

Kyung Hyun Min, Hyun Su Min, Hong Jae Lee, Dong Jin Park, Ji Young Yhee, Kwangmeyung Kim, Ick Chan Kwon, Seo Young Jeong, Oscar F. Silvestre, Xiaoyuan Chen, Yu Shik Hwang, Eun Cheol Kim, Sang Cheon Lee

Research output: Contribution to journalArticle

123 Scopus citations

Abstract

We report a theranostic nanoparticle that can express ultrasound (US) imaging and simultaneous therapeutic functions for cancer treatment. We developed doxorubicin-loaded calcium carbonate (CaCO3) hybrid nanoparticles (DOX-CaCO3-MNPs) through a block copolymer templated in situ mineralization approach. The nanoparticles exhibited strong echogenic signals at tumoral acid pH by producing carbon dioxide (CO2) bubbles and showed excellent echo persistence. In vivo results demonstrated that the DOX-CaCO3-MNPs generated CO2 bubbles at tumor tissues sufficient for echogenic reflectivity under a US field. In contrast, the DOX-CaCO3-MNPs located in the liver or tumor-free subcutaneous area did not generate the CO2 bubbles necessary for US contrast. The DOX-CaCO3-MNPs could also trigger the DOX release simultaneously with CO2 bubble generation at the acidic tumoral environment. The DOX-CaCO3-MNPs displayed effective antitumor therapeutic activity in tumor-bearing mice. The concept described in this work may serve as a useful guide for development of various theranostic nanoparticles for US imaging and therapy of various cancers.

Original languageEnglish (US)
Pages (from-to)134-145
Number of pages12
JournalACS nano
Volume9
Issue number1
DOIs
StatePublished - Jan 27 2015

Keywords

  • carbon dioxide
  • drug delivery
  • mineralization
  • nanobubble
  • theranostics
  • ultrasound

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