Prostate cancer-targeted imaging using magnetofluorescent polymeric nanoparticles functionalized with bombesin.
OBJECTIVE
In this work, the aim was to prepare and characterize a magnetofluorescent polymeric nanoparticle for prostate cancer imaging in vivo.


METHODS
Glycol chitosan (GC) was chemically modified with N-acetyl histidine (NAHis) as a hydrophobic moiety, and bombesin (BBN) was conjugated to the hydrophobically modified GC for use in targeting gastric-releasing peptide receptors (GRPR) overexpressed in prostate cancer cells. NAHis-GC conjugates were labeled with the near-infrared (NIR) fluorophore Cy5.5 (C-NAHis-GC conjugate).


RESULTS
BBN-conjugated C-NAHis-GC nanoparticles (BC-NAHis-GC nanoparticles) showed significantly higher binding to the PC3 cell surface than nanoparticles without BBN, and the cellular binding was clearly inhibited by BBN. The tumor-to-muscle ratios of C- and BC-NAHis-GC nanoparticles were 2.26 +/- 0.66 and 5.37 +/- 0.43, respectively. The tumor accumulation of BC-NAHis-GC nanoparticles was clearly reduced by co-injection of BBN. Further, iron oxide nanoparticles (IO) were loaded into BC-NAHis-GC nanoparticles to investigate the possibility of use as a probe for MRI. IO-BC-NAHis-GC nanoparticles were well observed in the PC3 cells, and the blocking with BBN significantly reduced the cellular binding of the nanoparticles.


CONCLUSIONS
These results demonstrate that the BBN conjugation to NAHis-GC nanoparticles improves their tumor accumulation in PC3-bearing mice in comparison to nanoparticles without BBN, suggesting that BC-NAHis-GC nanoparticles may be useful for prostate cancer imaging.
Lee
Chang-Moon
CM
Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, 634-18, Geumam-2 dong, Dukjin-gu, Jeonju, Jeonbuk, 561-712, Republic of Korea.
Jeong
Hwan-Jeong
HJ
Cheong
Su-Jin
SJ
Kim
Eun-Mi
EM
Kim
Dong Wook
DW
Lim
Seok Tae
ST
Sohn
Myung-Hee
MH
D000818:Animals; D001839:Bombesin / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D005260:Female; D005453:Fluorescence; D008280:Magnetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D018004:Receptors, Bombesin / Q000378:metabolism*
D018377:Neurotransmitter Agents; D018004:Receptors, Bombesin; C118638:glycol-chitosan; D048271:Chitosan; D001839:Bombesin