Carbon Dioxide-Generating PLG Nanoparticles for Controlled Anti-Cancer Drug Delivery
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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 Wordscancer drug delivery gas-generation polymer nanoparticle
PLG nanoparticle containing mineralized calcium carbonate
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
Non-gas-generating PLG nanoparticle
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.