Poly-lactic-co-glycolic acid Nanoformulation of Small Molecule Antagonist GANT61 for Cancer Annihilation by Modulating Hedgehog Pathway
Journal Title: NanoWorld Journal - Year 2017, Vol 3, Issue 1
Abstract
Targeting the self-renewal pathways (SRPs) in cancer has become one of the futuristic treatment strategies in order to prevent cancer relapse and drug resistance. One of the embryonic SRPs, Hedgehog (Hh) pathway is found to be aberrantly active in most of the cancers such as basal cell carcinoma, brain tumors, pancreas, prostate, leukemia’s to name a few. GANT61, a hexahydropyrimidine derivative is a specific GLI1 inhibitor of the Hedgehog pathway known for its anticancer activity and also its ability to inhibit the self-renewal properties of cancer stem cells (CSCs). However, its clinical efficacy is limited due to its low water solubility, bioavailability and poor permeability. The objective of this paper is to present an effective nano drug delivery system for GANT61 to improve its water solubility, enhanced drug delivery with low toxicity to the healthy cells without compromising on the native behavior of the drug. We synthesized GANT61 PLGA nanoparticles through single emulsion solvent evaporation technique and studied the physicochemical properties of the nanoparticles. GANT61 PLGA NPs showed cytotoxicity against the cancer cells, with only minimal effect towards the normal cells. Furthermore, we also analyzed the inhibition of GLI1 nuclear translocation by GANT61 PLGA NPs using immunofluorescence staining. Our studies report the successful encapsulation of GANT61 inside polymeric nanoparticles with improved aqueous solubility, which resulted in cancer cells cytotoxicity and elimination of CSCs.
Authors and Affiliations
Ankita Borah, Vivekanandan Palaninathan, Aswathy Ravindran Girija, Sivakumar Balasubramanian, Ankit K. Rochani, Toru Maekawa, D. Sakthi Kumar
Keywords
Related Articles
- EP ID EP223516
- DOI 10.17756/nwj.2017-038
- Views 103
- Downloads 0
Langmuir-Blodgett Technology for Drugs Production and Delivery: Insights and Implications from an In Silico Study
Insulin dynameomics here reported as a database pertaining to a series of Molecular Dynamics (MD) ran for Protein Data Bank (PDB) entries consisting in bioinformatics and molecular dynamics simulation of Langmuir-Blodget...
Science and Technology for A Sustainable Human Development
At the end of the NanoWorld Conference in San Francisco 25 April 2018 it was decided to formalize the move of the NanoWorld Journal Headquarter from Texas (USA) at United Scientific Group to Bergamo (Europe) at Fondazion...
Magnetophoresis of Superparamagnetic Nanoparticles Applied to the Extraction of Lanthanide Ions in the Presence of Magnetic Field
Magnetic migration (magnetophoresis) and extraction of Dy3+ ions by magnetite (Fe3O4) nanoparticles functionalized with diethylenetriaminepentaacetic acid (MagNP@DTPA) were probed, using an analytical balance and an exte...
A Worldwide Strategy for Energy, Environment and Space Should Emerge in Paris as the Priority of Humanity: A Review
Climate change, need for alternative energy and increasing asteroids in size and number represent key issues yielding growing challenges that must be tackled with more determination by the world community. The meeting se...
Surface Modification Efficiency of Titanium-based Particles with an Alkyl Phosphate
This article reports the efficiency of surface modification of titanium particles based on an alkyl phosphate. Different techniques were used to evaluate the behavior of the samples after modification, in terms of better...