Anti-CRLF2 antibody-armored biodegradable nanoparticles for childhood B-ALL

Rekha Raghunathan, Swetha Mahesula, Kranthi Kancharla, Preethi Janardhanan, Yeshwant L A Jadhav, Robert Nadeau, German P. Villa, Robert L. Cook, Colleen M. Witt, Jonathan A Gelfond, Thomas G. Forsthuber, William E. Haskins

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

B-precursor acute lymphoblastic leukemia (B-ALL) lymphoblast (blast) internalization of anti-cytokine receptor-like factor 2 (CRLF2) antibody-armored biodegradable nanoparticles (AbBNPs) are investigated. First, AbBNPsaere synthesized by adsorbing anti-CRLF2 antibodies to poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles of various sizes and antibody surface density (Ab/BNP) ratios. Second, AbBNPs are incubated with CRLF2-overexpressing (CRLF2+) or control blasts. Third, internalization of AbBNPs by blasts is evaluated by multicolor flow cytometry as a function of receptor expression, AbBNP size, and Ab/BNP ratio. Results from these experiments are confirmed by electron microscopy, fluorescence microscopy, and Western blotting. The optimal size and Ab/BNP for internalization of AbBNPs by CRLF2+ blasts is 50 nm with 10 Ab/BNP and 100 nm with 25 Ab/BNP. These studies show that internalization of AbBNPs in childhood B-ALL blasts is AbBNP size- and Ab/BNP ratio-dependent. All AbBNP combinations are non-cytotoxic. It is also shown that CD47 is very slightly up-regulated by blasts exposed to AbBNPs. CD47 is "the marker of self" overexpressed by blasts to escape phagocytosis, or "cellular devouring", by beneficial macrophages. The results indicate that precise engineering of AbBNPs by size and Ab/BNP ratio may improve the internalization and selectivity of future biodegradable nanoparticles for the treatment of leukemia patients, including drug-resistant minority children and Down's syndrome patients with CRLF2+B-ALL.

Original languageEnglish (US)
Pages (from-to)355-364
Number of pages10
JournalParticle and Particle Systems Characterization
Volume30
Issue number4
DOIs
StatePublished - Apr 2013

Fingerprint

Cytokine Receptors
leukemias
antibodies
Antibodies
Nanoparticles
nanoparticles
blasts
Cytokines
macrophages
cytometry
Flow cytometry
Macrophages
Fluorescence microscopy
minorities
markers
Electron microscopy
escape
electron microscopy
drugs
selectivity

Keywords

  • antibodies
  • biodegradable nanoparticles
  • biomedical applications
  • cancer health disparity
  • childhood leukemia

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Chemistry(all)
  • Materials Science(all)

Cite this

Raghunathan, R., Mahesula, S., Kancharla, K., Janardhanan, P., Jadhav, Y. L. A., Nadeau, R., ... Haskins, W. E. (2013). Anti-CRLF2 antibody-armored biodegradable nanoparticles for childhood B-ALL. Particle and Particle Systems Characterization, 30(4), 355-364. https://doi.org/10.1002/ppsc.201200125

Anti-CRLF2 antibody-armored biodegradable nanoparticles for childhood B-ALL. / Raghunathan, Rekha; Mahesula, Swetha; Kancharla, Kranthi; Janardhanan, Preethi; Jadhav, Yeshwant L A; Nadeau, Robert; Villa, German P.; Cook, Robert L.; Witt, Colleen M.; Gelfond, Jonathan A; Forsthuber, Thomas G.; Haskins, William E.

In: Particle and Particle Systems Characterization, Vol. 30, No. 4, 04.2013, p. 355-364.

Research output: Contribution to journalArticle

Raghunathan, R, Mahesula, S, Kancharla, K, Janardhanan, P, Jadhav, YLA, Nadeau, R, Villa, GP, Cook, RL, Witt, CM, Gelfond, JA, Forsthuber, TG & Haskins, WE 2013, 'Anti-CRLF2 antibody-armored biodegradable nanoparticles for childhood B-ALL', Particle and Particle Systems Characterization, vol. 30, no. 4, pp. 355-364. https://doi.org/10.1002/ppsc.201200125
Raghunathan R, Mahesula S, Kancharla K, Janardhanan P, Jadhav YLA, Nadeau R et al. Anti-CRLF2 antibody-armored biodegradable nanoparticles for childhood B-ALL. Particle and Particle Systems Characterization. 2013 Apr;30(4):355-364. https://doi.org/10.1002/ppsc.201200125
Raghunathan, Rekha ; Mahesula, Swetha ; Kancharla, Kranthi ; Janardhanan, Preethi ; Jadhav, Yeshwant L A ; Nadeau, Robert ; Villa, German P. ; Cook, Robert L. ; Witt, Colleen M. ; Gelfond, Jonathan A ; Forsthuber, Thomas G. ; Haskins, William E. / Anti-CRLF2 antibody-armored biodegradable nanoparticles for childhood B-ALL. In: Particle and Particle Systems Characterization. 2013 ; Vol. 30, No. 4. pp. 355-364.
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