Targeting mantle cell lymphoma with anti-SYK nanoparticles

Ingrid Cely, Seang Yiv, Qian Yin, Anoush Shahidzadeh, Li Tang, Jianjun Cheng, Fatih M. Uckun

Research output: Contribution to journalArticlepeer-review


The pentapeptide mimic 1,4-bis(9-O-dihydroquinidinyl)phthalazine / hydroquinidine 1,4-phathalazinediyl diether ("compound 61") (C-61) is the first reported inhibitor targeting the P-site of SYK. Here we report a nanotechnology platform to target C-61 to mantle cell lymphoma (MCL) cells. Liposomal nanoparticles (NP) loaded with C-61 were prepared using the standard thin film evaporation method. The entrapment of C-61 was obtained using the pH gradient procedure with lactobionic acid (LBA) being used as a low pH buffer inside the NP. Formulation F6A was selected as a lead candidate for further biological testing. The average diameter, zeta potential and C-61 content of the F6A NP was 40 nm, 0.1 mV, and 12.6 mg/ml, respectively. F6A induces apoptosis in SYK+ but not SYKleukemia/ lymphoma cells. We also evaluated the cytotoxic activity of F6A in the context of an in vitro artificial bone marrow assay platform based on a 3D scaffold with inverted colloidal crystal geometry mimicking the structural topology of actual bone marrow matrix. The ability of C-61 to induce apoptosis in ALL-1 cells was not adversely affected by the scaffolds. F6A, but not the drug-free NP formulation F6B, caused apoptosis of MCL cell lines MAVER-1 and MINO within 24h. Further development of rationally designed SYK inhibitors and their nanoscale formulations may provide the foundation for therapeutic innovation against a broad spectrum of lymphoid malignancies, including MCL.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalJournal of Analytical Oncology
Issue number1
StatePublished - 2012
Externally publishedYes


  • Cancer
  • Kinase
  • Leukemia
  • Lymphoma
  • Nanotechnology
  • Oncology
  • Personalized medicine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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