期刊
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
卷 11, 期 3, 页码 392-402出版社
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2015.1911
关键词
Cancer Nanomedicine; alpha(5)beta(1)-Integrins; Fibrinogen-graft-PNVCL Nanogels; Thermo-Sensitive; Lower Critical Solution Temperature; Multi Drug Effect
资金
- Department of Biotechnology (DBT), Government of India under a center grant of the Nanoscience and Nanotechnology Initiative program [BT/PR10850/NNT/28/127/2008]
- Council of Scientific and Industrial Research (CSIR) [9/963 (0017)2K11-EMR1]
This study aims at the targeted delivery of 5-fluorouracil (5-FU) and Megestrol acetate (Meg) loaded fibrinogen-graft-poly(N-Vinyl caprolactam) nanogels (5-FU/Meg-fib-graft-PNVCL NGs) toward alpha(5)beta(1)-integrins receptors expressed on breast cancer cells to have enhanced anti-cancer effect in vitro. To achieve this aim, we developed biocompatible thermo-responsive fib-graft-PNVCL NGs using fibrinogen and carboxyl terminated PNVCL via EDC/ NHS amidation reaction. The Lower Critical Solution Temperature (LCST) of fib-graft-PNVCL could be tuned according to PNVCL/fibrinogen compositions. The 100-120 nm sized nanogels of fib-graft-PNVCL (LCST= 35 +/- 1 degrees C) was prepared using CaCl2 cross-linker. The 5-FU/Meg-fib-graft-PNVCL NGs showed a particle size of 150-170 nm size. The drug loading efficiency with 5-FU was 62% while Meg showed 74%. The 5-FU and Meg release was prominent above LCST than below LCST. The multi drug loaded fib-graft-PNVCL NGs showed enhanced toxicity, apoptosis and uptake by breast cancer (MCF-7) cells compared to their individual doses above their LCST. The in vivo assessment in Swiss albino mice showed sustained release of Meg and 5-FU as early as 3 days, confirming the therapeutic efficiency of the formulation. These results demonstrate an enhanced platform for the future animal studies on breast tumor xenograft model.
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