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Poly-lactic-co-glycolic acid Nanoformulation of Small Molecule Antagonist GANT61 for Cancer Annihilation by Modulating Hedgehog Pathway – NanoWorld Journal

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class="attachment-content-single size-content-single wp-post-image" alt="" srcset="https://jnanoworld.com/wp-content/uploads/2017/07/5.jpg 260w, https://jnanoworld.com/wp-content/uploads/2017/07/5-120x67.jpg 120w" sizes="(max-width: 260px) 100vw, 260px"/></div> <p class="entry-meta"> </p> <div class="entry-content clearfix"> <div class="italics"><i>Ankita Borah, Vivekanandan Palaninathan, Aswathy Ravindran Girija, Sivakumar Balasubramanian, Ankit K. Rochani, Toru Maekawa and D. Sakthi Kumar</i></div> <div class="italics"></div> <div class="italics"></div> <div>&nbsp;</div> <div> <p><strong>Abstract</strong></p> </div> <p>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鈥檚 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.</p> <div> <strong>Published on:</strong> February 02, 2017<br/> <strong>doi:</strong>聽10.17756/nwj.2017-038<br/> <strong>Citation:</strong>聽 Borah A, Palaninathan V, Girija AR, Balasubramanian S, Rochani AK, et al. 2017. Poly-lactic-co-glycolic acid Nanoformulation of Small Molecule Antagonist GANT61 for Cancer Annihilation by Modulating Hedgehog Pathway. <em>NanoWorld J</em> 3(1): 1-10. </div> <div class="italics">&nbsp;</div> <div class="pdfdownloadlink"><img class="alignleft size-full wp-image-507" style="margin: 4px -5px 4px 5px;" src="http://jnanoworld.com/wp-content/uploads/2017/04/pdf-icon-24-e1509106685135-1.png" alt="" width="16" height="16"/><div class="sdm_download_link"><a href="https://jnanoworld.com/?smd_process_download=1&download_id=1184" class="sdm_download green" title="nwj-038-ankita-borah" target="_self">PDF (Download Full text)</a></div><span style="margin-top: 0.8%; display: inline-block;"><img class="alignleft size-full wp-image-497" style="margin: 0 7px;" src="http://jnanoworld.com/wp-content/uploads/2017/04/html-icon-24-e1509106669974.png" alt="" width="16" height="16"/><a href="http://jnanoworld.com/articles/v3n1/nwj-038-ankita-borah.html" target="_blank" rel="noopener 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