Pharmaceutical Research

, 35:59 | Cite as

Carbon Dioxide-Generating PLG Nanoparticles for Controlled Anti-Cancer Drug Delivery

  • Hyeon Jin Jang
  • Eun Ju Jeong
  • Kuen Yong Lee
Research Paper



Poly(D,L-lactide-co-glycolide) (PLG) nanoparticles containing doxorubicin and mineralized calcium carbonate were fabricated and their anti-tumor efficacy was tested using a neuroblastoma-bearing mouse model.


PLG nanoparticles were prepared by a double emulsion (water-in-oil-in-water; W/O/W) method. Calcium carbonate was mineralized within the PLG nanoparticles during the emulsion process. Rabies virus glycoprotein (RVG) peptide was chemically introduced to the surface of the PLG nanoparticles as a targeting moiety against neuroblastoma. The cytotoxicity and cellular uptake characteristics of these nanoparticles were investigated in vitro. Moreover, their therapeutic efficacy was evaluated using a tumor-bearing mouse model.


Mineralized calcium carbonate in PLG nanoparticles was ionized at acidic pH and generated carbon dioxide gas, which resultantly accelerated the release of doxorubicin from the nanoparticles. RVG peptide-modified, gas-generating PLG nanoparticles showed a significantly enhanced targeting ability to neuroblastoma and an increased therapeutic efficacy in vivo as compared with free doxorubicin.


Targeting ligand-modified polymer nanoparticles containing both anti-cancer drug and mineralized calcium carbonate could be useful for cancer treatment.

Key Words

cancer drug delivery gas-generation polymer nanoparticle 





1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide


PLG nanoparticle containing mineralized calcium carbonate


2-(N-Morpholino)ethanesulfonic acid


3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide






Phosphate-buffered saline




Non-gas-generating PLG nanoparticle


Poly(vinyl alcohol)


Rabies virus glycoprotein


Acknowledgments and Disclosures

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT & Future Planning (MSIP) (NRF-2016R1A2A2A10005086). The authors have declared no conflict of interest.

Supplementary material

11095_2018_2359_MOESM1_ESM.docx (4.6 mb)
ESM 1 (DOCX 4730 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Hyeon Jin Jang
    • 1
  • Eun Ju Jeong
    • 1
  • Kuen Yong Lee
    • 1
    • 2
  1. 1.Department of BioengineeringHanyang UniversitySeoulRepublic of Korea
  2. 2.Institute of Nano Science and TechnologyHanyang UniversitySeoulRepublic of Korea

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