Bioengineering functional copolymers. XXI. Synthesis of a novel end carboxyl-trithiocarbonate functionalized poly(maleic anhydride) and its interaction with cancer cells
Yükleniyor...
Tarih
2012
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Pergamon-Elsevier Science Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
A novel carboxyl-trithiocarbonate functionalized polymer with a highly selective antitumor activity was synthesized by a reversible addition-fragmentation chain transfer (RAFT) polymerization of maleic anhydride (MA) with benzoyl peroxide as an initiator and S-1-dodecyl-S-(alpha, alpha'-dimethyl-alpha ''-acetic acid)-trithiocarbonate as a RAFT agent with the aim to design and synthesize an effective anticancer agent with minimum side effects. The structure, molecular weights and composition of synthesized polymers were investigated by H-1 (C-13) NMR, MALDI-TOF-MS and GPC analyzes. It was demonstrated that RAFT polymerization of MA was accompanied by a partially controlled decarboxylation of anhydride units and the formation of conjugated double bond fragments in backbone macromolecular chains. The mechanism of interaction of pristine RAFT agent and PMA-RAFT polymer with cancer (HeLa human cervix carcinoma) and normal (L929 Fibroblast) cells was investigated by using a combination of chemical, biochemical, statistical, spectroscopic (SEM and fluorescence inverted microscope) and real-time analysis (RTCA) methods. PMA-RAFT exhibited higher and selective cytotoxicity, apoptotic and necrotic effects toward HeLa cells at relatively low concentrations (around 7.5-75 mu g mL (1), IC50 = 11.183 mu g mL (1)) and toward Fibroblast cells at high concentrations (IC50 > 100 mu g mL (1)). The observed highly selective antitumor activity render PMA-RAFT polymers as promising candidates for the utilization in cancer chemotherapy. (C) 2012 Elsevier Ltd. All rights reserved.
Açıklama
Anahtar Kelimeler
Synthesis, RAFT polymerization, Multifunctional polymer, Cancer cells, Cytoxicity, Apoptotic and necrotic effects
Kaynak
Bioorganic & Medicinal Chemistry
WoS Q Değeri
Q2
Scopus Q Değeri
Q1
Cilt
20
Sayı
16
Künye
closedAccess
