期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 193, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.colsurfb.2020.111135
关键词
MMP2; Enzyme responsive; AS1411
资金
- Mashhad University of Medical Sciences [961096]
In the current study, polyethylene glycol (PEG) was linked to polylactide (PLA) through the synthetic peptide PVGLIG which can be selectively cleaved by the tumor-associated matrix metalloproteinase 2 (MMP-2) enzyme. The synthesized chimeric triblock polymer of PEG-b-PVGLIG-PLA was implemented to form nanoscale self-assemble chimeric polymersomes. The hydrophobic SN38 was loaded into polymersomes with 70.3% +/- 3.0% encapsulation efficiency demonstrating monodispersed spherical morphologies with 172 +/- 30 nm dimension. The prepared chimeric polymersomal formulation provided controlled release of SN38 at physiological condition while illustrating seven-folds higher release rate when exposed to MMP-2 enzyme. At the next stage, AS1411 aptamer was conjugated onto the surface of MMP-2 responsive polymersomal formulation in order to provide guided drug delivery against nucleolin positive cells. In vitro cellular toxicity assay against C26 cell line (nucleolin positive) demonstrated significantly higher toxicity of targeted formulation in comparison with non-targeted one in low SN38 concentrations (0.15-1.25 mu g/mL). In vivo study in mice bearing subcutaneous C26 tumor showed higher therapeutic index for MMP-2 responsive chimeric polymersomal formulation of SN38 in comparison with non-responsive one. On the other hand, AS1411 aptamer-targeted MMP-2 responsive chimeric polymersomal formulation exhibited highest therapeutic index compared to other groups. It could be concluded that the targeted chimeric polymersomes bearing both cleavable peptide sequence between their blocks and targeting ligand on their surface, provide favorable characteristics as an ideal delivery system against cancer.
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