Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

Noriko Satake, Joyce S 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

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

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.

Original languageEnglish (US)
Title of host publicationProceedings of SPIE - The International Society for Optical Engineering
Volume8031
DOIs
StatePublished - 2011
EventMicro- and Nanotechnology Sensors, Systems, and Applications III - Orlando, FL, United States
Duration: Apr 25 2011Apr 29 2011

Other

OtherMicro- and Nanotechnology Sensors, Systems, and Applications III
CountryUnited States
CityOrlando, FL
Period4/25/114/29/11

Keywords

  • acute lymphoblastic leukemia
  • integrin
  • leukemia-specific ligand
  • nanoparticles
  • targeted therapy

ASJC Scopus subject areas

  • Applied Mathematics
  • Computer Science Applications
  • Electrical and Electronic Engineering
  • Electronic, Optical and Magnetic Materials
  • Condensed Matter Physics

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  • Cite this

    Satake, N., Lee, J. S., Xiao, K., Luo, J., Sarangi, S., Chang, A., McLaughlin, B., Zhou, P., Kenney, E., Kraynov, L., Arnott, S., McGee, J., Nolta, J., & Lam, K. (2011). Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia. In Proceedings of SPIE - The International Society for Optical Engineering (Vol. 8031). [80311U] https://doi.org/10.1117/12.885550