Targeted MMP-2 responsive SN38-loaded polymersomes for colorectal cancer therapy
Paper ID : 1382-ICNS
Pouria Ramezani *1, Mohammad Ramezani2, Mona Alibolandi3
1Mashhad University of Medical Sciences
2Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences
3Department of Pharmaceutical Biotechnology, Mashhad University od Medical Sciences
In the current study, polylactide (PLA) was conjugated to polyethylene glycol (PEG) via a small peptide sequence, PVGLIG which is a substrate for the tumor-associated enzyme matrix metalloproteinase-2 enzyme. The chimeric triblock polymer of PEG-b-PVGLIG-PLA was used to form nanoscale self-assembled polymersomes. Subsequently, the anticancer drug, SN38 was loaded into polymersomes through single emulsion method and the prepared polymersomes were characterized by DLS, AFM and SEM. The hydrophobic SN38 was loaded with 70 encapsulation efficiency and 5% loading content providing monodispersed spherical nanoparticles with 172 nm dimension. The prepared polymeromes provided sustained release of SN38 under physiological condition but augmented release following exposure to MMP-2 enzyme. Afterwards, AS1411 aptamer was conjugated to the surface of the polymersomes in order to provide guided drug delivery. In vitro cytotoxicity against C26 cells (+nucleolin) demonstrated significantly higher toxicity for the targeted formulation in comparison with the non-targeted one. In vivo study employing C26 tumor model in mice showed higher therapeutic index of MMP-2 responsive polymersomal formulation in comparison with the non-responsive one. It could be concluded that the prepared polymersomes bearing cleavable peptide sequence between their blocks and targeting ligand on their surface, provide interesting features as intelligent drug delivery system against cancer.
Polymersome; SN38; MMP2; Enzyme responsive; AS1411
Status : Abstract Accepted (Oral Presentation)