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Enhanced Intracellular Delivery of BCG Cell Wall Skeleton into Bladder Cancer Cells Using Liposomes Functionalized with Folic Acid and Pep-1 Peptide

Although bacillus Calmette–Guérin cell wall skeleton (BCG-CWS) might function as a potential substitute for live BCG, its use in the treatment of bladder cancer remains limited owing to issues such as insolubility and micrometer-size following exposure to an aqueous environment. Thus, to develop a n...

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Autores principales: Yoon, Ho Yub, Yang, Hee Mang, Kim, Chang Hyun, Goo, Yoon Tae, Hwang, Gwang Yong, Chang, In Ho, Whang, Young Mi, Choi, Young Wook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970232/
https://www.ncbi.nlm.nih.gov/pubmed/31817179
http://dx.doi.org/10.3390/pharmaceutics11120652
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author Yoon, Ho Yub
Yang, Hee Mang
Kim, Chang Hyun
Goo, Yoon Tae
Hwang, Gwang Yong
Chang, In Ho
Whang, Young Mi
Choi, Young Wook
author_facet Yoon, Ho Yub
Yang, Hee Mang
Kim, Chang Hyun
Goo, Yoon Tae
Hwang, Gwang Yong
Chang, In Ho
Whang, Young Mi
Choi, Young Wook
author_sort Yoon, Ho Yub
collection PubMed
description Although bacillus Calmette–Guérin cell wall skeleton (BCG-CWS) might function as a potential substitute for live BCG, its use in the treatment of bladder cancer remains limited owing to issues such as insolubility and micrometer-size following exposure to an aqueous environment. Thus, to develop a novel nanoparticulate system for efficient BCG-CWS delivery, liposomal encapsulation was carried out using a modified emulsification-solvent evaporation method (targets: Size, <200 nm; encapsulation efficiency, ~60%). Further, the liposomal surface was functionalized with specific ligands, folic acid (FA), and Pep-1 peptide (Pep1), as targeting and cell-penetrating moieties, respectively. Functionalized liposomes greatly increased the intracellular uptake of BCG-CWS in the bladder cancer cell lines, 5637 and MBT2. The immunoactivity was verified through elevated cytokine production and a THP-1 migration assay. In vivo antitumor efficacy revealed that the BCG-CWS-loaded liposomes effectively inhibited tumor growth in mice bearing MBT2 tumors. Dual ligand-functionalized liposome was also superior to single ligand-functionalized liposomes. Immunohistochemistry supported the enhanced antitumor effect of BCG-CWS, with IL-6 production and CD4 infiltration. Thus, we conclude that FA- and Pep1-modified liposomes encapsulating BCG-CWS might be a good candidate for bladder cancer treatment with high target selectivity.
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spelling pubmed-69702322020-02-04 Enhanced Intracellular Delivery of BCG Cell Wall Skeleton into Bladder Cancer Cells Using Liposomes Functionalized with Folic Acid and Pep-1 Peptide Yoon, Ho Yub Yang, Hee Mang Kim, Chang Hyun Goo, Yoon Tae Hwang, Gwang Yong Chang, In Ho Whang, Young Mi Choi, Young Wook Pharmaceutics Article Although bacillus Calmette–Guérin cell wall skeleton (BCG-CWS) might function as a potential substitute for live BCG, its use in the treatment of bladder cancer remains limited owing to issues such as insolubility and micrometer-size following exposure to an aqueous environment. Thus, to develop a novel nanoparticulate system for efficient BCG-CWS delivery, liposomal encapsulation was carried out using a modified emulsification-solvent evaporation method (targets: Size, <200 nm; encapsulation efficiency, ~60%). Further, the liposomal surface was functionalized with specific ligands, folic acid (FA), and Pep-1 peptide (Pep1), as targeting and cell-penetrating moieties, respectively. Functionalized liposomes greatly increased the intracellular uptake of BCG-CWS in the bladder cancer cell lines, 5637 and MBT2. The immunoactivity was verified through elevated cytokine production and a THP-1 migration assay. In vivo antitumor efficacy revealed that the BCG-CWS-loaded liposomes effectively inhibited tumor growth in mice bearing MBT2 tumors. Dual ligand-functionalized liposome was also superior to single ligand-functionalized liposomes. Immunohistochemistry supported the enhanced antitumor effect of BCG-CWS, with IL-6 production and CD4 infiltration. Thus, we conclude that FA- and Pep1-modified liposomes encapsulating BCG-CWS might be a good candidate for bladder cancer treatment with high target selectivity. MDPI 2019-12-04 /pmc/articles/PMC6970232/ /pubmed/31817179 http://dx.doi.org/10.3390/pharmaceutics11120652 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yoon, Ho Yub
Yang, Hee Mang
Kim, Chang Hyun
Goo, Yoon Tae
Hwang, Gwang Yong
Chang, In Ho
Whang, Young Mi
Choi, Young Wook
Enhanced Intracellular Delivery of BCG Cell Wall Skeleton into Bladder Cancer Cells Using Liposomes Functionalized with Folic Acid and Pep-1 Peptide
title Enhanced Intracellular Delivery of BCG Cell Wall Skeleton into Bladder Cancer Cells Using Liposomes Functionalized with Folic Acid and Pep-1 Peptide
title_full Enhanced Intracellular Delivery of BCG Cell Wall Skeleton into Bladder Cancer Cells Using Liposomes Functionalized with Folic Acid and Pep-1 Peptide
title_fullStr Enhanced Intracellular Delivery of BCG Cell Wall Skeleton into Bladder Cancer Cells Using Liposomes Functionalized with Folic Acid and Pep-1 Peptide
title_full_unstemmed Enhanced Intracellular Delivery of BCG Cell Wall Skeleton into Bladder Cancer Cells Using Liposomes Functionalized with Folic Acid and Pep-1 Peptide
title_short Enhanced Intracellular Delivery of BCG Cell Wall Skeleton into Bladder Cancer Cells Using Liposomes Functionalized with Folic Acid and Pep-1 Peptide
title_sort enhanced intracellular delivery of bcg cell wall skeleton into bladder cancer cells using liposomes functionalized with folic acid and pep-1 peptide
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970232/
https://www.ncbi.nlm.nih.gov/pubmed/31817179
http://dx.doi.org/10.3390/pharmaceutics11120652
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