PAMAM-camptothecin conjugate inhibits proliferation and induces nuclear fragmentation in colorectal carcinoma cells.
PAMAM-camptothecin conjugate inhibits proliferation and induces nuclear fragmentation in colorectal carcinoma cells.
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DOI：
10.1007/s11095-010-0179-6
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发表时间：
2010-11
影响因子：
3.7
通讯作者：
Ghandehari, Hamidreza
中科院分区：
文献类型：
--
作者：
Thiagarajan, Giridhar;Ray, Abhijit;Malugin, Alexander;Ghandehari, Hamidreza
目的合成聚（酰胺胺）树状大分子-喜树碱（PAMAM-CPT）偶联物，并研究其对人结肠癌细胞（HCT-116）的抑制作用。CPT与胺封端的PAMAM的连接是通过琥珀酸-甘氨酸接头来促进的。对结合物进行了表征，以确定不存在小分子量杂质、大小和药物含量。研究了偶联物在PBS和生长培养基中的稳定性及其对HCT-116的体外活性。研究了PAMAM-CPT处理后的细胞周期阻滞和核碎裂。该偶联物在生理pH（7.4）下在PBS和生长培养基（含10%FBS）中稳定，48 h时分别最小释放4%和6%药物。PAMAM-CPT抑制HCT-116细胞增殖，IC 50值为1.6±0.3 μM。偶联物诱导细胞周期停滞的迹象，高达68%的细胞阻滞在G2期。用PAMAM-CPT处理的细胞的共聚焦图像表明核碎裂和凋亡小体的形成。结果表明，PAMAM-CPT缀合物在体外对结肠直肠癌细胞具有活性，抑制其生长并诱导核碎裂。再加上将大分子治疗剂靶向肿瘤的能力，这种缀合物显示出癌症化疗的前景。
To synthesize and characterize a poly (amido amine) dendrimer-camptothecin (PAMAM-CPT) conjugate and evaluate its activity on human colorectal carcinoma cells (HCT-116). The attachment of CPT to amine-terminated PAMAM was facilitated through a succinic acid-glycine linker. The conjugate was characterized for absence of small molecular weight impurities, size and drug content. Stability of the conjugate in PBS and growth media and its in vitro activity on HCT-116 were studied. Cell cycle arrest and nuclear fragmentation upon PAMAM-CPT treatment were investigated. The conjugate was stable under physiological pH (7.4) in PBS and in growth media (with 10% FBS) with minimal release of 4% and 6% drug, respectively, at 48 h. PAMAM-CPT inhibited proliferation of HCT-116 cells with an IC50 value of 1.6±0.3 μM. The conjugate induced signs of cell cycle arrest with up to 68% of cells blocked in the G2 phase. Confocal images of cells treated with PAMAM-CPT suggest nuclear fragmentation and formation of apoptotic bodies. Results show that the PAMAM-CPT conjugate was active against colorectal cancer cells in vitro, inhibiting their growth and inducing nuclear fragmentation. Coupled with the ability to target macromolecular therapeutics to tumors, this conjugate shows promise for cancer chemotherapy.
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影响因子：
10.8
作者：
El-Sayed, M;Ginski, M;Ghandehari, H
通讯作者：
Ghandehari, H
影响因子：
5.8
作者：
Milhem, OM;Myles, C;D'Emanuele, A
通讯作者：
D'Emanuele, A
影响因子：
2.3
作者：
Malik, N;Evagorou, EG;Duncan, R
通讯作者：
Duncan, R
影响因子：
3.7
作者：
Pan, Huaizhong;Kopeckova, Pavla;Kopecek, Jindrich
通讯作者：
Kopecek, Jindrich
影响因子：
5.8
作者：
Najlah, Mohammad;Freeman, Sally;D'Emanuele, Antony
通讯作者：
D'Emanuele, Antony