کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10228814 | 496 | 2012 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Anti-CD20 multivalent HPMA copolymer-Fabâ² conjugates for the direct induction of apoptosis
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی شیمی
بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
A hybrid biomimetic system comprising high-molecular-weight, linear copolymer of N-(2-hydroxypropyl)methacrylamide (HPMA) grafted with multiple FabⲠfragments of anti-CD20 monoclonal antibody (mAb) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization followed by attachment of FabⲠfragments via thioether bonds. Exposure of human non-Hodgkin's lymphoma (NHL) Raji B cells to the multivalent conjugates resulted in crosslinking of CD20 receptors and commencement of apoptosis. Five conjugates with varying molecular weight and valence (amount of FabⲠper polymer chain) were synthesized. One of the copolymers contained enzyme degradable peptide sequences (GFLG) in the backbone. The multivalency led to higher avidity and apoptosis induction compared to unconjugated whole mAb. Time-dependent studies showed that the cytotoxicity of conjugates exhibited a slower onset at shorter exposure times than mAb hyper-crosslinked with a secondary Ab; however, at longer time intervals the HPMA copolymer conjugates achieved significantly higher biological efficacies. In addition, study of the relationship between the structure of conjugates and Raji B cell apoptosis revealed that both valency and polymer molecular weight influenced biological activities, while insertion of peptide sequences into the backbone was not a factor in vitro.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 33, Issue 29, October 2012, Pages 7174-7181
Journal: Biomaterials - Volume 33, Issue 29, October 2012, Pages 7174-7181
نویسندگان
Te-Wei Chu, Jiyuan Yang, JindÅich KopeÄek,