title: Multifunctional targeting micelle nanocarriers with both imaging and therapeutic potential for bladder cancer.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of California- Davis, Sacramento, CA 95817, USA.
authors: Tzu-Yin
authors: TY
authors: Lin
authors: Hongyong
authors: H
authors: Zhang
authors: Juntao
authors: J
authors: Luo
authors: Yuanpei
authors: Y
authors: Li
authors: Tingjuan
authors: T
authors: Gao
authors: Primo N
authors: PN
authors: Lara
authors: Ralph
authors: R
authors: de Vere White
authors: Kit S
authors: KS
authors: Lam
authors: Chong-Xian
authors: CX
authors: Pan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008823:Micelles; C558117:PLZ4 peptide; D010456:Peptides, Cyclic; D017239:Paclitaxel; D003630:Daunorubicin