PMID- 23976822 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211021 IS - 0934-0866 (Print) IS - 1521-4117 (Electronic) IS - 0934-0866 (Linking) VI - 30 IP - 4 DP - 2013 Apr TI - Anti-CRLF2 Antibody-Armored Biodegradable Nanoparticles for Childhood B-ALL. PG - 355-364 AB - 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 con-firmed 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. FAU - Raghunathan, Rekha AU - Raghunathan R AD - Pediatric Biochemistry Laboratory Department of Chemistry-BSE 3.108A University of Texas at San Antonio One UTSA Circle, San Antonio, TX 78249, USA. FAU - Mahesula, Swetha AU - Mahesula S FAU - Kancharla, Kranthi AU - Kancharla K FAU - Janardhanan, Preethi AU - Janardhanan P FAU - Jadhav, Yeshwant L A AU - Jadhav YL FAU - Nadeau, Robert AU - Nadeau R FAU - Villa, German P AU - Villa GP FAU - Cook, Robert L AU - Cook RL FAU - Witt, Colleen M AU - Witt CM FAU - Gelfond, Jonathan A L AU - Gelfond JA FAU - Forsthuber, Thomas G AU - Forsthuber TG FAU - Haskins, William E AU - Haskins WE LA - eng GR - U54 RR022762/RR/NCRR NIH HHS/United States GR - L40 CA130418/CA/NCI NIH HHS/United States GR - P30 CA054174/CA/NCI NIH HHS/United States GR - U54 MD008149/MD/NIMHD NIH HHS/United States GR - G12 MD007591/MD/NIMHD NIH HHS/United States GR - G12 RR013646/RR/NCRR NIH HHS/United States PT - Journal Article PL - Germany TA - Part Part Syst Charact JT - Particle & particle systems characterization : measurement and description of particle properties and behavior in powders and other disperse systems JID - 9891749 PMC - PMC3746557 MID - NIHMS481324 EDAT- 2013/08/27 06:00 MHDA- 2013/08/27 06:01 PMCR- 2014/04/01 CRDT- 2013/08/27 06:00 PHST- 2013/08/27 06:00 [entrez] PHST- 2013/08/27 06:00 [pubmed] PHST- 2013/08/27 06:01 [medline] PHST- 2014/04/01 00:00 [pmc-release] AID - 10.1002/ppsc.201200125 [doi] PST - ppublish SO - Part Part Syst Charact. 2013 Apr;30(4):355-364. doi: 10.1002/ppsc.201200125.