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Proceedings Paper

Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia
Author(s): Noriko Satake; Joyce Lee; Kai Xiao; Juntao Luo; Susmita Sarangi; Astra Chang; Bridget McLaughlin; Ping Zhou; Elaina Kenney; Liliya Kraynov; Sarah Arnott; Jeannine McGee; Jan Nolta; Kit Lam
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Paper Abstract

The goal of our project is to develop a unique ligand-conjugated nanoparticle (NP) therapy against childhood acute lymphoblastic leukemia (ALL). LLP2A, discovered by Dr. Kit Lam, is a high-affinity and high-specificity peptidomimetic ligand against an activated α4β1 integrin. Our study using 11 fresh primary ALL samples (10 precursor B ALL and 1 T ALL) showed that childhood ALL cells expressed activated α4β1 integrin and bound to LLP2A. Normal hematopoietic cells such as activated lymphocytes and monocytes expressed activated α4β1 integrin; however, normal hematopoietic stem cells showed low expression of α4β1 integrin. Therefore, we believe that LLP2A can be used as a targeted therapy for childhood ALL. The Lam lab has developed novel telodendrimer-based nanoparticles (NPs) which can carry drugs efficiently. We have also developed a human leukemia mouse model using immunodeficient NOD/SCID/IL2Rγ null mice engrafted with primary childhood ALL cells from our patients. LLP2A-conjugated NPs will be evaluated both in vitro and in vivo using primary leukemia cells and this mouse model. NPs will be loaded first with DiD near infra-red dye, and then with the chemotherapeutic agents daunorubicin or vincristine. Both drugs are mainstays of current chemotherapy for childhood ALL. Targeting properties of LLP2A-conjugated NPs will be evaluated by fluorescent microscopy, flow cytometry, MTS assay, and mouse survival after treatment. We expect that LLP2A-conjugated NPs will be preferentially delivered and endocytosed to leukemia cells as an effective targeted therapy.

Paper Details

Date Published: 13 May 2011
PDF: 5 pages
Proc. SPIE 8031, Micro- and Nanotechnology Sensors, Systems, and Applications III, 80311U (13 May 2011); doi: 10.1117/12.885550
Show Author Affiliations
Noriko Satake, Univ. of California, Davis (United States)
Joyce Lee, Univ. of California, Davis (United States)
Kai Xiao, Univ. of California, Davis (United States)
Juntao Luo, Univ. of California, Davis (United States)
Susmita Sarangi, Univ. of California, Davis (United States)
Astra Chang, Univ. of California, Davis (United States)
Bridget McLaughlin, Univ. of California, Davis (United States)
Ping Zhou, Univ. of California, Davis (United States)
Elaina Kenney, Univ. of California, Davis (United States)
Liliya Kraynov, Univ. of California, Davis (United States)
Sarah Arnott, Univ. of California, Davis (United States)
Jeannine McGee, Univ. of California, Davis (United States)
Jan Nolta, Univ. of California, Davis (United States)
Kit Lam, Univ. of California, Davis (United States)


Published in SPIE Proceedings Vol. 8031:
Micro- and Nanotechnology Sensors, Systems, and Applications III
Thomas George; M. Saif Islam; Achyut K. Dutta, Editor(s)

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