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Prostate Cancer-Targeted Imaging Using Magnetofluorescent Polymeric Nanoparticles Functionalized with Bombesin

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Abstract

Purpose

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.

Conclusion

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.

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ACKNOWLEDGMENTS

This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health, Welfare and Family Affairs, Republic of Korea (0620220 and 0720420). This work was also supported by the Nuclear R&D Program through the Korea Science and Engineering Foundation funded by the Ministry of Science & Technology (contract grant numbers: 20090062447).

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Authors and Affiliations

  1. 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

    Chang-Moon Lee, Hwan-Jeong Jeong, Su-Jin Cheong, Eun-Mi Kim, Dong Wook Kim, Seok Tae Lim & Myung-Hee Sohn

  2. Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, 561-712, Republic of Korea

    Chang-Moon Lee, Hwan-Jeong Jeong, Su-Jin Cheong, Eun-Mi Kim, Dong Wook Kim, Seok Tae Lim & Myung-Hee Sohn

  3. Cyclotron Research Center, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, 561-712, Republic of Korea

    Chang-Moon Lee, Hwan-Jeong Jeong, Su-Jin Cheong, Eun-Mi Kim, Dong Wook Kim, Seok Tae Lim & Myung-Hee Sohn

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  1. Chang-Moon Lee
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  2. Hwan-Jeong Jeong
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Correspondence to Hwan-Jeong Jeong.

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Lee, CM., Jeong, HJ., Cheong, SJ. et al. Prostate Cancer-Targeted Imaging Using Magnetofluorescent Polymeric Nanoparticles Functionalized with Bombesin. Pharm Res 27, 712–721 (2010). https://doi.org/10.1007/s11095-010-0072-3

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  • DOI: https://doi.org/10.1007/s11095-010-0072-3

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