Journal
RSC ADVANCES
Volume 7, Issue 17, Pages 10333-10344Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c6ra27114f
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Funding
- National Natural Science Foundation of China [21472126, 21672151]
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Folate-or L-5-methyltetrahydrofolate-modified poly(ethyleneimine) (PEI) functionalized magnetic microgels (MP-PNAAEF or MP-PNAAEM) for targeted delivery to positive folate-receptor [FR(+)] cancer cells have been successfully prepared. Transmission electron microscopy (TEM) shows that the Fe3O4 nanoparticles are well covered with PNAAEF microgels, exhibiting regular spherical structures with few agglomerates. The mean size of the magnetic microgels measured by dynamic light scattering (DLS) is dependent on temperature and pH, and they exhibit good thermosensitivity as well as pH sensitivity. The research on drug loading and the drug release behavior of magnetic microgels shows that the MPPNAAEF and MP-PNAAEM microgels are capable of loading more doxorubicin hydrochloride (DOX) than MP-PNAAE under appropriate conditions, and in vitro release is faster at pH 4.5 than at pH 7.4, and faster at 45 degrees C than at 37 degrees C. In vitro cytotoxicity of these microgels to Hela cells [FR(+)] and L02 cells [FR(-)] were evaluated, and all microgels were nontoxic up to a concentration of 15 mu g mL(-1) toward Hela cells and 30 mg mL(-1) toward L02 cells. Specifically, the cellular uptake of MP-PNAAE, MP-PNAAEF and MPPNAAEM was observed with both cell lines. FA and MTHF modification on the MP-PNAAE increased the microgel uptake by Hela cells, but not by the L02 cells, as demonstrated by fluorescence microscopy; thus, the MTHF may possess remarkable properties toward Hela cells. Meanwhile, the DOX-loaded MPPNAAEF and MP-PNAAEM microgels present greater cytotoxicity to Hela cells than free DOX and DOX-loaded MP-PNAAE microgels. The results suggest that MTHF may represent a potential ligand for targeted anticancer drug delivery, and the MP-PNAAEF and MP-PNAAEM magnetic microgels may represent a potential tumor targeting drug carrier.
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