Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules

Shayak Samaddar, Joshua Mazur, Devin Boehm, David H Thompson Department of Chemistry, Purdue University, Bindley Bioscience Center, West Lafayette, Indiana 47906, USACorrespondence: David H ThompsonDepartment of Chemistry, Purdue University, Bindley Bioscience Center, 1203 W. State St., West Lafayet...

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Autores principales:	Samaddar S, Mazur J, Boehm D, Thompson DH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	dual delivery bladder cancer gene therapy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c4b90ff1c7434650815473deb7054870
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spelling	oai:doaj.org-article:c4b90ff1c7434650815473deb70548702021-12-02T08:51:55ZDevelopment And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules1178-2013https://doaj.org/article/c4b90ff1c7434650815473deb70548702019-12-01T00:00:00Zhttps://www.dovepress.com/development-and-in-vitro-characterization-of-bladder-tumor-cell-target-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Shayak Samaddar, Joshua Mazur, Devin Boehm, David H Thompson Department of Chemistry, Purdue University, Bindley Bioscience Center, West Lafayette, Indiana 47906, USACorrespondence: David H ThompsonDepartment of Chemistry, Purdue University, Bindley Bioscience Center, 1203 W. State St., West Lafayette, Indiana 47906, USATel +1 765-494-0386Email davethom@purdue.eduBackground: Bladder cancer is the fourth most common cancer in men and eleventh most common in women. Combination therapy using a gene and chemotherapeutic drug is a potentially useful strategy for treating bladder cancer in cases where a synergistic benefit can be achieved successfully. This approach relies on developing drug combinations using carrier systems that can load both hydrophilic genes and hydrophobic drugs. Ideally, the formulation for carrier system should be free of traditional high shear techniques such as sonication and extrusion to reduce shear-induced nucleic acid strand breakage. Moreover, the system should be able to protect the nucleic acid from enzymatic attack and deliver it specifically to the tumor site.Materials and methods: A dual payload carrier system that was formulated using a simple flow mixing technique to complex anionic plasmid (EGFP-NLS) using a cationic polymer (CD-PEI2.5kD) followed by coating of the polyplex using lipid membranes. The resulting lipid-coated polyplex (LCP) formulations are targeted to bladder cancer cells by employing a bacterial adhesive peptide sequence, RWFV, that targets the LCP to the tumor stroma for efficiently delivering reporter plasmid, EGFP-NLS and a model small molecule drug, pyrene, to the cancer cells.Results: Encapsulation efficiency of the peptide targeted carrier for the plasmid was 50% ± 0.4% and for pyrene it was 16% ± 0.4%. The ability of the targeted LCP to transfect murine bladder cancer cells was 4-fold higher than LCP bearing a scrambled peptide sequence. Fluorescence of cells due to pyrene delivery was highest after 4 hrs using targeted LCP. Finally, we loaded the peptide targeted LCP with anti-cancer agent, curcumin. The targeted formulation of curcumin resulted in only 45% viable cancer cells at a concentration of 5 μg/mL, whereas the empty and non-targeted formulations did not result any significant cell death.Conclusion: These results demonstrate the specificity of the targeting peptide sequence in engaging tumor cells and the utility of the developed carrier platform to deliver a dual payload to bladder tumor cells.Keywords: dual delivery, bladder cancer, gene therapy  Samaddar SMazur JBoehm DThompson DHDove Medical Pressarticledual deliverybladder cancergene therapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 9547-9561 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	dual delivery bladder cancer gene therapy Medicine (General) R5-920
spellingShingle	dual delivery bladder cancer gene therapy Medicine (General) R5-920 Samaddar S Mazur J Boehm D Thompson DH Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules
description	Shayak Samaddar, Joshua Mazur, Devin Boehm, David H Thompson Department of Chemistry, Purdue University, Bindley Bioscience Center, West Lafayette, Indiana 47906, USACorrespondence: David H ThompsonDepartment of Chemistry, Purdue University, Bindley Bioscience Center, 1203 W. State St., West Lafayette, Indiana 47906, USATel +1 765-494-0386Email davethom@purdue.eduBackground: Bladder cancer is the fourth most common cancer in men and eleventh most common in women. Combination therapy using a gene and chemotherapeutic drug is a potentially useful strategy for treating bladder cancer in cases where a synergistic benefit can be achieved successfully. This approach relies on developing drug combinations using carrier systems that can load both hydrophilic genes and hydrophobic drugs. Ideally, the formulation for carrier system should be free of traditional high shear techniques such as sonication and extrusion to reduce shear-induced nucleic acid strand breakage. Moreover, the system should be able to protect the nucleic acid from enzymatic attack and deliver it specifically to the tumor site.Materials and methods: A dual payload carrier system that was formulated using a simple flow mixing technique to complex anionic plasmid (EGFP-NLS) using a cationic polymer (CD-PEI2.5kD) followed by coating of the polyplex using lipid membranes. The resulting lipid-coated polyplex (LCP) formulations are targeted to bladder cancer cells by employing a bacterial adhesive peptide sequence, RWFV, that targets the LCP to the tumor stroma for efficiently delivering reporter plasmid, EGFP-NLS and a model small molecule drug, pyrene, to the cancer cells.Results: Encapsulation efficiency of the peptide targeted carrier for the plasmid was 50% ± 0.4% and for pyrene it was 16% ± 0.4%. The ability of the targeted LCP to transfect murine bladder cancer cells was 4-fold higher than LCP bearing a scrambled peptide sequence. Fluorescence of cells due to pyrene delivery was highest after 4 hrs using targeted LCP. Finally, we loaded the peptide targeted LCP with anti-cancer agent, curcumin. The targeted formulation of curcumin resulted in only 45% viable cancer cells at a concentration of 5 μg/mL, whereas the empty and non-targeted formulations did not result any significant cell death.Conclusion: These results demonstrate the specificity of the targeting peptide sequence in engaging tumor cells and the utility of the developed carrier platform to deliver a dual payload to bladder tumor cells.Keywords: dual delivery, bladder cancer, gene therapy
format	article
author	Samaddar S Mazur J Boehm D Thompson DH
author_facet	Samaddar S Mazur J Boehm D Thompson DH
author_sort	Samaddar S
title	Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules
title_short	Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules
title_full	Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules
title_fullStr	Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules
title_full_unstemmed	Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules
title_sort	development and in vitro characterization of bladder tumor cell targeted lipid-coated polyplex for dual delivery of plasmids and small molecules
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/c4b90ff1c7434650815473deb7054870
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Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules

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