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Multifunctional targeting micelle nanocarriers with both imaging and therapeutic potential for bladder cancer

Authors Lin TY, Zhang H, Luo J, Li Y, Gao T, Lara Jr PN, de Vere White R, Lam KS, Pan CX

Received 28 October 2011

Accepted for publication 9 December 2011

Published 6 June 2012 Volume 2012:7 Pages 2793—2804

DOI https://doi.org/10.2147/IJN.S27734

Review by Single-blind

Peer reviewer comments 3

Tzu-yin Lin,1 Hongyong Zhang,1 Juntao Luo,2,5 Yuanpei Li,2 Tingjuan Gao,3 Primo N Lara Jr,1,4,6 Ralph de Vere White,4 Kit S Lam,1,2 Chong-Xian Pan,1,3,6
1Division of Hematology and Oncology, Department of Internal Medicine, 2Department of Biochemistry and Molecular Medicine, 3NSF Center for Biophotonics Science and Technology, School of Medicine, 4Department of Urology, University of California-Davis, Sacramento, CA, 5Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, 6VA Northern California Health Care System, Mather, CA, USA

Background: We previously developed a bladder cancer-specific ligand (PLZ4) that can specifically bind to both human and dog bladder cancer cells in vitro and in vivo. We have also developed a micelle nanocarrier drug-delivery system. Here, we assessed whether the targeting micelles decorated with PLZ4 on the surface could specifically target dog bladder cancer cells.
Materials and methods: Micelle-building monomers (ie, telodendrimers) were synthesized through conjugation of polyethylene glycol with a cholic acid cluster at one end and PLZ4 at the other, which then self-assembled in an aqueous solution to form micelles. Dog bladder cancer cell lines were used for in vitro and in vivo drug delivery studies.
Results: Compared to nontargeting micelles, targeting PLZ4 micelles (23.2 ± 8.1 nm in diameter) loaded with the imaging agent DiD and the chemotherapeutic drug paclitaxel or daunorubicin were more efficient in targeted drug delivery and more effective in cell killing in vitro. PLZ4 facilitated the uptake of micelles together with the cargo load into the target cells. We also developed an orthotopic invasive dog bladder cancer xenograft model in mice. In vivo studies with this model showed the targeting micelles were more efficient in targeted drug delivery than the free dye (14.3×; P < 0.01) and nontargeting micelles (1.5×; P < 0.05).
Conclusion: Targeting micelles decorated with PLZ4 can selectively target dog bladder cancer cells and potentially be developed as imaging and therapeutic agents in a clinical setting. Preclinical studies of targeting micelles can be performed in dogs with spontaneous bladder cancer before proceeding with studies using human patients.

Keywords: bladder urothelial carcinoma, nanoparticle, bladder cancer-specific peptide, targeted therapy, diagnostic imaging

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