Targeting Mantle Cell Lymphoma with Anti-SYK Nanoparticles

Authors

  • Ingrid Cely Developmental Therapeutics Program, Children’s Hospital Los Angeles, Children’s Center for Cancer and Blood Diseases, Los Angeles, CA 90027, USA
  • Seang Yiv Developmental Therapeutics Program, Children’s Hospital Los Angeles, Children’s Center for Cancer and Blood Diseases, Los Angeles, CA 90027, USA
  • Qian Yin Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA
  • Anoush Shahidzadeh Developmental Therapeutics Program, Children’s Hospital Los Angeles, Children’s Center for Cancer and Blood Diseases, Los Angeles, CA 90027, USA
  • Li Tang Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA
  • Jianjun Cheng Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA
  • Fatih M. Uckun Developmental Therapeutics Program, Children’s Hospital Los Angeles, Children’s Center for Cancer and Blood Diseases, Los Angeles, CA 90027, USA

DOI:

https://doi.org/10.6000/1927-7229.2012.01.01.1

Keywords:

Nanotechnology, Personalized medicine, lymphoma, leukemia, cancer, oncology, kinase

Abstract

 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 SYK- leukemia/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.

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Published

2012-01-28

How to Cite

Ingrid Cely, Seang Yiv, Qian Yin, Anoush Shahidzadeh, Li Tang, Jianjun Cheng, & Fatih M. Uckun. (2012). Targeting Mantle Cell Lymphoma with Anti-SYK Nanoparticles . Journal of Analytical Oncology, 1(1), 1–9. https://doi.org/10.6000/1927-7229.2012.01.01.1

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