Targeted Herceptin-dextran iron oxide nanoparticles for noninvasive imaging of HER2/neu receptors using MRI.
A novel magnetic resonance imaging (MRI) contrast agent containing Herceptin is reported. The surfaces of superparamagnetic iron oxide nanoparticles were modified with dextran and conjugated with Herceptin (Herceptin-nanoparticles) to improve their dispersion, magnetization, and targeting of the specific receptors on cells. From analytical results, we found that Herceptin-nanoparticles were well dispersed in solutions of various pH range, and had no hysteresis, high saturation magnetization (80 emu/g), and low cytotoxicity to a variety of cells. Notably, the magnetic resonance enhancements for the different breast cancer cell lines (BT-474, SKBR-3, MDA-MB-231, and MCF-7) are proportional to the HER2/neu expression level in vitro. When Herceptin-nanoparticles were administered to mice bearing breast tumor allograft by intravenous injection, the tumor site was detected in T (2)-weighted magnetic resonance images as a 45% enhancement drop, indicating a high level of accumulation of the contrast agent within the tumor sites. Therefore, targeting of cancer cells was observed by in vitro and in vivo MRI studies using Herceptin-nanoparticles contrast agent. In addition, Herceptin-nanoparticles enhancing the magnetic resonance signal intensity were sufficient to detect the cell lines with a low level of HER2/neu expression.
Chen
Ting-Jung
TJ
Department of Biological Science and Technology, National Chiao Tung University, 75 Bo-Ai Street, Hsinchu, 300, Taiwan.
Cheng
Tsan-Hwang
TH
Chen
Chiao-Yun
CY
Hsu
Sodio C N
SC
Cheng
Tian-Lu
TL
Liu
Gin-Chung
GC
Wang
Yun-Ming
YM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D003911:Dextrans; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005260:Female; D052203:Ferrosoferric Oxide; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry*; D010087:Oxides / Q000008:administration & dosage / Q000009:adverse effects / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000378:metabolism*; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007501:Iron; D058185:Magnetite Nanoparticles; D010087:Oxides; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C065507:ferumoxides