Specific targeting to B cells by lipid-based nanoparticles conjugated with a novel CD22-ScFv
| Autor: | Himanshu Garg, Ryan Campbell-Massa, Xiaodong Xiao, Dimiter S. Dimitrov, Anu Puri, Kristin H. Loomis, Yang Feng, Amichai Yavlovich, Robert Blumenthal, Brandon Smith |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities 1 2-Dipalmitoylphosphatidylcholine Cell Survival Sialic Acid Binding Ig-like Lectin 2 T-Lymphocytes Clinical Biochemistry Biology Article Cell Line Pathology and Forensic Medicine chemistry.chemical_compound Antigen Immunotoxin hemic and lymphatic diseases medicine Humans Doxorubicin Molecular Biology Fluorescent Dyes B-Lymphocytes Liposome Phosphatidylethanolamines Flow Cytometry Molecular biology Calcein chemistry Targeted drug delivery Liposomes Drug delivery Nanoparticles Drug carrier Single-Chain Antibodies medicine.drug |
| Zdroj: | Experimental and Molecular Pathology. 88:238-249 |
| ISSN: | 0014-4800 |
| DOI: | 10.1016/j.yexmp.2010.01.006 |
| Popis: | The CD22 antigen is a viable target for therapeutic intervention for B-cell lymphomas. Several therapeutic anti-CD22 antibodies as well as an anti-CD22-based immunotoxin (HA22) are currently under investigation in clinical settings. Coupling of anti-CD22 reagents with a nano-drug delivery vehicle is projected to significantly improve treatment efficacies. Therefore, we generated a mutant of the targeting segment of HA22 (a CD22 scFv) to increase its soluble expression (mut-HA22), and conjugated it to the surface of sonicated liposomes to generate immunoliposomes (mut-HA22-liposomes). We examined liposome binding and uptake by CD22(+) B-lymphocytes (BJAB) by using calcein and/or rhodamine PE-labeled liposomes. We also tested the effect of targeting on cellular toxicity with doxorubicin-loaded liposomes. We report that: (i) Binding of mut-HA22-liposomes to BJAB cells was significantly greater than liposomes not conjugated with mut-HA22 (control liposomes), and mut-HA22-liposomes bind to and are taken in by BJAB cells in a dose and temperature-dependent manner, respectively; (ii) This binding occurred via the interaction with the cellular CD22 as pre-incubation of the cells with mut-HA22 blocked subsequent liposome binding; (iii) Intracellular localization of mut-HA22-liposomes at 37 degrees C but not at 4 degrees C indicated that our targeted liposomes were taken up through an energy dependent process via receptor-mediated endocytosis; and (iv) Mut-HA22-liposomes loaded with doxorubicin exhibited at least 2-3 fold more accumulation of doxorubicin in BJAB cells as compared to control liposomes. Moreover, these liposomes showed at least a 2-4 fold enhanced killing of BJAB or Raji cells (CD22(+)), but not SUP-T1 cells (CD22(-)). Taken together these data suggest that these 2nd-generation liposomes may serve as promising carriers for targeted drug delivery to treat patients suffering from B-cell lymphoma. |
| Databáze: | OpenAIRE |
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