Targeting pancreatic cancer with magneto-fluorescent theranostic gold nanoshells.
OBJECTIVE
We report a magneto-fluorescent theranostic nanocomplex targeted to neutrophil gelatinase-associated lipocalin (NGAL) for imaging and therapy of pancreatic cancer.


METHODS
Gold nanoshells resonant at 810 nm were encapsulated in silica epilayers doped with iron oxide and the near-infrared (NIR) dye indocyanine green, resulting in theranostic gold nanoshells (TGNS), which were subsequently conjugated with antibodies targeting NGAL in AsPC-1-derived xenografts in nude mice.


RESULTS
Anti-NGAL-conjugated TGNS specifically targeted pancreatic cancer cells in vitro and in vivo providing contrast for both NIR fluorescence and T2-weighted MRI with higher tumor contrast than can be obtained using long-circulating, but nontargeted, PEGylated nanoparticles. The nanocomplexes also enabled highly specific cancer cell death via NIR photothermal therapy in vitro.


CONCLUSIONS
TGNS with embedded NIR and magnetic resonance contrasts can be specifically targeted to pancreatic cancer cells with expression of early disease marker NGAL, and enable molecularly targeted imaging and photothermal therapy.
Division of Molecular Imaging, Department of Radiology, Baylor College of Medicine, Mail: BCM 360, One Baylor Plaza, Houston, TX 77030, USA and Department of Diagnostic Imaging, The Fourth Hospital of Hebei Medical University/Hebei Province Tumor Hospital, 12 Jiankang Road, Shijiazhuang, Hebei Province 050011, China.
Wenxue
W
Chen
Ciceron
C
Ayala-Orozco
Nrusingh C
NC
Biswal
Carlos
C
Perez-Torres
Marc
M
Bartels
Rizia
R
Bardhan
Gary
G
Stinnet
Xian-De
XD
Liu
Baoan
B
Ji
Amit
A
Deorukhkar
Lisa V
LV
Brown
Sushovan
S
Guha
Robia G
RG
Pautler
Sunil
S
Krishnan
Naomi J
NJ
Halas
Amit
A
Joshi
D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000627:therapeutic use; D006046:Gold / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D006979:Hyperthermia, Induced; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D059346:Magnets / Q000737:chemistry; D008819:Mice, Nude; D057145:Nanoshells / Q000737:chemistry / Q000627:therapeutic use*; D015513:Oncogene Proteins / Q000378:metabolism; D061848:Optical Imaging; D010179:Pancreas / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy*; D010789:Phototherapy
D000209:Acute-Phase Proteins; D003287:Contrast Media; D005456:Fluorescent Dyes; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse; D006046:Gold
MRI; nanoshells; noninvasive imaging; optical imaging; pancreatic cancer; photothermal