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 Citation (Scopus)

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

Fingerprint

leukemias
Leukemia
Acute
Therapy
Nanoparticles
therapy
Integrins
nanoparticles
Integrin
mice
Mouse
Cell
Ligands
cells
Peptidomimetics
drugs
Daunorubicin
Chemotherapy
Lymphocytes
Flow cytometry

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

Cite this

Satake, N., Lee, J. S., Xiao, K., Luo, J., Sarangi, S., Chang, A., ... 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

Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia. / Satake, Noriko; Lee, Joyce S; Xiao, Kai; Luo, Juntao; Sarangi, Susmita; Chang, Astra; McLaughlin, Bridget; Zhou, Ping; Kenney, Elaina; Kraynov, Liliya; Arnott, Sarah; McGee, Jeannine; Nolta, Jan; Lam, Kit.

Proceedings of SPIE - The International Society for Optical Engineering. Vol. 8031 2011. 80311U.

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

Satake, N, Lee, JS, 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, Micro- and Nanotechnology Sensors, Systems, and Applications III, Orlando, FL, United States, 4/25/11. https://doi.org/10.1117/12.885550
Satake N, Lee JS, Xiao K, Luo J, Sarangi S, Chang A et al. Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia. In Proceedings of SPIE - The International Society for Optical Engineering. Vol. 8031. 2011. 80311U https://doi.org/10.1117/12.885550
Satake, Noriko ; Lee, Joyce S ; Xiao, Kai ; Luo, Juntao ; Sarangi, Susmita ; Chang, Astra ; McLaughlin, Bridget ; Zhou, Ping ; Kenney, Elaina ; Kraynov, Liliya ; Arnott, Sarah ; McGee, Jeannine ; Nolta, Jan ; Lam, Kit. / Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia. Proceedings of SPIE - The International Society for Optical Engineering. Vol. 8031 2011.
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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.",
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