Pullulan-histone antibody nanoconjugates for the removal of chromatin fragments from systemic circulation

Abstract The billions of cells that die in the adult human body daily release considerable amounts of fragmented chromatin in the form of mono- and oligonucleosomes into the circulation in normal individuals, and in higher quantities in many disease conditions. Recent results suggest that circulatin...

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Bibliographic Details
Published in:Biomaterials 2013-09, Vol.34 (27), p.6328-6338
Main Authors: Rekha, M.R, Pal, Kavita, Bala, Preetam, Shetty, Mihir, Mittra, Indraneel, Bhuvaneshwar, G.S, Sharma, Chandra P
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Antibodies
Apoptosis
Biomedical materials
Cancer
Cell Line
Cells, Cultured
Chromatin
Chromatin - isolation & purification
Circulation
Dentistry
Doxorubicin
Fragments
Glucans - chemistry
Glucans - therapeutic use
Hep G2 Cells
Histone antibodies
Histones
Histones - immunology
Humans
Immunoconjugates - chemistry
Immunoconjugates - immunology
Immunoconjugates - therapeutic use
In vivo clearance
Mice
Mice, Inbred BALB C
Nanoconjugates
Nanoconjugates - chemistry
Nanoconjugates - therapeutic use
Nanostructure
Neutropenia - chemically induced
Neutropenia - drug therapy
Pullulan
Rats
Rats, Wistar
Sepsis - drug therapy
Sepsis - immunology
Surgical implants
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Summary:Abstract The billions of cells that die in the adult human body daily release considerable amounts of fragmented chromatin in the form of mono- and oligonucleosomes into the circulation in normal individuals, and in higher quantities in many disease conditions. Recent results suggest that circulating chromatin fragments (Cfs) especially from abnormal cells can spontaneously enter into healthy cells to damage their DNA and induce genomic instability. Furthermore, Cfs isolated from cancer patients may induce oncogenic transformation in the recipients' cells. Thus, it follows that if such Cfs emanating from apoptotic cells could be prevented from reaching other cells, it could potentially inhibit pathological conditions, including cancer. Here we have developed pullulan based histone antibody nanoconjugates for the removal of Cfs. Nanoconjugates were developed and various physico-chemical characterizations were carried out. The efficacy of these nanoconjugates on removing Cfs was evaluated both in vitro and in vivo . Our results indicate that nanoconjugates may have therapeutic value in the efficient removal of Cfs, reducing inflammation and fatality in a mouse model of sepsis, and in preventing neutropenia following treatment with Adriamycin.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2013.05.019