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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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

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Abbreviations

DOX:

Doxorubicin

EDC:

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

mCNP:

PLG nanoparticle containing mineralized calcium carbonate

MES:

2-(N-Morpholino)ethanesulfonic acid

MTT:

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

N2a:

Neuro-2a

NHS:

N-Hydroxysulfosuccinimide

PBS:

Phosphate-buffered saline

PLG:

Poly(D,L-lactide-co-glycolide)

PNP:

Non-gas-generating PLG nanoparticle

PVA:

Poly(vinyl alcohol)

RVG:

Rabies virus glycoprotein

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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.

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Authors and Affiliations

  1. Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea

    Hyeon Jin Jang, Eun Ju Jeong & Kuen Yong Lee

  2. Institute of Nano Science and Technology, Hanyang University, Seoul, 04763, Republic of Korea

    Kuen Yong Lee

Authors
  1. Hyeon Jin Jang
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  2. Eun Ju Jeong
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Correspondence to Kuen Yong Lee.

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Jang, H.J., Jeong, E.J. & Lee, K.Y. Carbon Dioxide-Generating PLG Nanoparticles for Controlled Anti-Cancer Drug Delivery. Pharm Res 35, 59 (2018). https://doi.org/10.1007/s11095-018-2359-8

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