Hyeon Jin Jang1, Eun Ju Jeong1, Kuen Yong Lee2,3. 1. Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea. 2. Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea. leeky@hanyang.ac.kr. 3. Institute of Nano Science and Technology, Hanyang University, Seoul, 04763, Republic of Korea. leeky@hanyang.ac.kr.
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.
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.
Entities:
Keywords:
cancer; drug delivery; gas-generation; polymer nanoparticle
Authors: Malgosia M Pakulska; Irja Elliott Donaghue; Jaclyn M Obermeyer; Anup Tuladhar; Christopher K McLaughlin; Tyler N Shendruk; Molly S Shoichet Journal: Sci Adv Date: 2016-05-27 Impact factor: 14.136