Enhancement of irradiation effects on cancer cells by cross-linked dextran-coated iron oxide (CLIO) nanoparticles.
We investigated iron oxide nanoparticles with two different surface modifications, dextran coating and cross-linked dextran coating, showing that their different internalization affects their capability to enhance radiation damage to cancer cells. The internalization was monitored with an ultrahigh resolution transmission x-ray microscope (TXM), indicating that the differences in the particle surface charge play an essential role and dominate the particle-cell interaction. We found that dextran-coated iron oxide nanoparticles cannot be internalized by HeLa and EMT-6 cells without being functionalized with amino groups (the cross-linked dextran coating) that modify the surface potential from -18 mV to 13.4 mV. The amount of cross-linked dextran-coated iron oxide nanoparticles uptaken by cancer cells reached its maximum, 1.33 x 10(9) per HeLa cell, when the co-culture concentration was 40 microg Fe mL(-1) or more. Standard tests indicated that these internalized nanoparticles increased the damaging effects of x-ray irradiation, whereas they are by themselves biocompatible. These results could lead to interesting therapy applications; furthermore, iron oxide also produces high contrast for magnetic resonance imaging (MRI) in the diagnosis and therapy stages.
Huang
Fu-Kuo
FK
Department of Chemical and Materials Engineering, National Yunlin University of Science and Technology, 123, University Rd, Sec. 3, Douliu, Yunlin 64002, Taiwan, Republic of China.
Chen
Wen-Chang
WC
Lai
Sheng-Feng
SF
Liu
Chi-Jen
CJ
Wang
Cheng-Liang
CL
Wang
Chang-Hai
CH
Chen
Hsiang-Hsin
HH
Hua
Tzu-En
TE
Cheng
Yi-Yun
YY
Wu
M K
MK
Hwu
Y
Y
Yang
Chung-Shi
CS
Margaritondo
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001692:Biological Transport / Q000187:drug effects; D002277:Carcinoma / Q000532:radiotherapy* / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D018920:Coculture Techniques; D003911:Dextrans / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D006367:HeLa Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D014964:X-Ray Therapy / Q000379:methods
D000970:Antineoplastic Agents; D003911:Dextrans; D005290:Ferric Compounds; C000499:ferric oxide