title: 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 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.
authors.affiliation: Biosurface Technology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Poojappura, Thiruvananthapuram 695012, Kerala, India.
authors.forename: M R
authors.initials: MR
authors.lastname: Rekha
authors.forename: Kavita
authors.initials: K
authors.lastname: Pal
authors.forename: Preetam
authors.initials: P
authors.lastname: Bala
authors.forename: Mihir
authors.initials: M
authors.lastname: Shetty
authors.forename: Indraneel
authors.initials: I
authors.lastname: Mittra
authors.forename: G S
authors.initials: GS
authors.lastname: Bhuvaneshwar
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Sharma
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002478:Cells, Cultured; D002843:Chromatin / Q000302:isolation & purification*; D004317:Doxorubicin; D005936:Glucans / Q000737:chemistry / Q000627:therapeutic use*; D056945:Hep G2 Cells; D006657:Histones / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D058726:Nanoconjugates / Q000737:chemistry / Q000627:therapeutic use*; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology
chemical_list: D002843:Chromatin; D005936:Glucans; D006657:Histones; D018796:Immunoconjugates; D058726:Nanoconjugates; D004317:Doxorubicin; C009109:pullulan