Hollow superparamagnetic iron oxide nanoshells as a hydrophobic anticancer drug carrier: intracelluar pH-dependent drug release and enhanced cytotoxicity.
With curcumin and doxorubicin (DOX) base as model drugs, intracellular delivery of hydrophobic anticancer drugs by hollow structured superparamagnetic iron oxide (SPIO) nanoshells (hydrodynamic diameter: 191.9 ± 2.6 nm) was studied in glioblastoma U-87 MG cells. SPIO nanoshell-based encapsulation provided a stable aqueous dispersion of the curcumin. After the SPIO nanoshells were internalized by U-87 MG cells, they localized at the acidic compartments of endosomes and lysosomes. In endosome/lysosome-mimicking buffers with a pH of 4.5-5.5, pH-dependent drug release was observed from curcumin or DOX loaded SPIO nanoshells (curcumin/SPIO or DOX/SPIO). Compared with the free drug, the intracellular curcumin content delivered via curcumin/SPIO was 30 fold higher. Increased intracellular drug content for DOX base delivered via DOX/SPIO was also confirmed, along with a fast intracellular DOX release that was attributed to its protonation in the acidic environment. DOX/SPIO enhanced caspase-3 activity by twofold compared with free DOX base. The concentration that induced 50% cytotoxic effect (CC(50)) was 0.05 ± 0.03 μg ml(-1) for DOX/SPIO, while it was 0.13 ± 0.02 μg ml(-1) for free DOX base. These results suggested SPIO nanoshells might be a promising intracellular carrier for hydrophobic anticancer drugs.
Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, P. R. China.
Xiao-Ming
XM
Zhu
Jing
J
Yuan
Ken Cham-Fai
KC
Leung
Siu-Fung
SF
Lee
Kathy W Y
KW
Sham
Christopher H K
CH
Cheng
Doris W T
DW
Au
Gao-Jun
GJ
Teng
Anil T
AT
Ahuja
Yi-Xiang J
YX
Wang
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D004337:Drug Carriers / Q000737:chemistry*; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008247:Lysosomes / Q000378:metabolism; D008280:Magnetics; D008856:Microscopy, Fluorescence; D057145:Nanoshells / Q000737:chemistry*; D014162:Transfection
D004337:Drug Carriers; D004317:Doxorubicin