Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

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

doi:10.1117/12.885550

13 May 2011 Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

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

Author Affiliations +

Proceedings Volume 8031, Micro- and Nanotechnology Sensors, Systems, and Applications III; 80311U (2011) https://doi.org/10.1117/12.885550
Event: SPIE Defense, Security, and Sensing, 2011, Orlando, Florida, United States

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.

Citation Download Citation

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, and Kit Lam "Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia", Proc. SPIE 8031, Micro- and Nanotechnology Sensors, Systems, and Applications III, 80311U (13 May 2011); https://doi.org/10.1117/12.885550

ACCESS THE FULL ARTICLE

INSTITUTIONAL
Select your institution to access the SPIE Digital Library.

SELECT YOUR INSTITUTION

PERSONAL
Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.

PERSONAL SIGN IN

No SPIE Account? Create one

PURCHASE THIS CONTENT

SUBSCRIBE TO DIGITAL LIBRARY

50 downloads per 1-year subscription

Members: $195

Non-members: $335 ADD TO CART

25 downloads per 1 - year subscription

Members: $145

Non-members: $250 ADD TO CART

PURCHASE SINGLE ARTICLE

Includes PDF, HTML & Video, when available