Sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy

Min Beom Heo,1,2 Sun-Young Kim,1 Wan Soo Yun,3 Yong Taik Lim1 1SKKU Advanced Institute of Nanotechnology (SAINT), School of Chemical Engineering, Sungkyunkwan University, Suwon, 2Center for Nanosafety Metrology, Division of Convergence Technology, Korea Research Institute of Standards and Science, D...

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Autores principales:	Heo MB, Kim SY, Yun WS, Lim YT
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d65312e1aa5a403197423da01c26a875
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spelling	oai:doaj.org-article:d65312e1aa5a403197423da01c26a8752021-12-02T07:36:51ZSequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy1178-2013https://doaj.org/article/d65312e1aa5a403197423da01c26a8752015-09-01T00:00:00Zhttps://www.dovepress.com/sequential-delivery-of-an-anticancer-drug-and-combined-immunomodulator-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Min Beom Heo,1,2 Sun-Young Kim,1 Wan Soo Yun,3 Yong Taik Lim1 1SKKU Advanced Institute of Nanotechnology (SAINT), School of Chemical Engineering, Sungkyunkwan University, Suwon, 2Center for Nanosafety Metrology, Division of Convergence Technology, Korea Research Institute of Standards and Science, Daejeon, 3Department of Chemistry, Sungkyunkwan University, Suwon, Republic of Korea Abstract: Chemoimmunotherapy combines chemotherapy based on anticancer drugs with immunotherapy based on immune activators to eliminate or inhibit the growth of cancer cells. In this study, water-insoluble paclitaxel (PTX) was dispersed in water using hyaluronic acid (HA) to generate a tumor-associated antigen in the tumor microenvironment. Cytosine–phosphate–guanosine oligodeoxynucleotides (CpG ODNs) were used to enhance the T helper (Th) 1 immune response. However, CpG ODNs also induced the secretion of interleukin-10 (IL-10) that reduces the Th1 response and enhances the T helper 2 (Th2) response. Therefore, RNA interference was used to downregulate IL-10 secretion from bone marrow-derived dendritic cells (BMDCs). For the combined immunomodulation of BMDCs, we fabricated two types of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing CpG ODNs to activate BMDCs via Toll-like receptor 9 (CpG ODN-encapsulated PLGA NPs, PCNs) or a small interfering RNA to silence IL-10 (IL-10 small interfering RNA-encapsulated PLGA NPs, PINs). Treatment of BMDCs with both types of PLGA NPs increased the Th1/Th2 cytokine (IL-12/IL-10) expression ratio, which is important for the effective induction of an antitumor immune response. After primary injection with the HA/PTX complex, the tumor-associated antigen was generated and taken up by tumor-recruited BMDCs. After a secondary injection with immunomodulating PCNs and PINs, the BMDCs became activated and migrated to the tumor-draining lymph nodes. As a result, the combination of chemotherapy using the HA/PTX complex and immunotherapy using PCNs and PINs not only efficiently inhibited tumor growth but also increased the animal survival rate. Taken together, our results suggest that the sequential treatment of cancer cells with a chemotherapeutic agent and immunomodulatory nanomaterials represents a promising strategy for efficient cancer therapy. Keywords: nanoparticles, chemoimmunotherapy, dendritic cells, cancer, siRNAHeo MBKim SYYun WSLim YTDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 5981-5993 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Heo MB Kim SY Yun WS Lim YT Sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy
description	Min Beom Heo,1,2 Sun-Young Kim,1 Wan Soo Yun,3 Yong Taik Lim1 1SKKU Advanced Institute of Nanotechnology (SAINT), School of Chemical Engineering, Sungkyunkwan University, Suwon, 2Center for Nanosafety Metrology, Division of Convergence Technology, Korea Research Institute of Standards and Science, Daejeon, 3Department of Chemistry, Sungkyunkwan University, Suwon, Republic of Korea Abstract: Chemoimmunotherapy combines chemotherapy based on anticancer drugs with immunotherapy based on immune activators to eliminate or inhibit the growth of cancer cells. In this study, water-insoluble paclitaxel (PTX) was dispersed in water using hyaluronic acid (HA) to generate a tumor-associated antigen in the tumor microenvironment. Cytosine–phosphate–guanosine oligodeoxynucleotides (CpG ODNs) were used to enhance the T helper (Th) 1 immune response. However, CpG ODNs also induced the secretion of interleukin-10 (IL-10) that reduces the Th1 response and enhances the T helper 2 (Th2) response. Therefore, RNA interference was used to downregulate IL-10 secretion from bone marrow-derived dendritic cells (BMDCs). For the combined immunomodulation of BMDCs, we fabricated two types of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing CpG ODNs to activate BMDCs via Toll-like receptor 9 (CpG ODN-encapsulated PLGA NPs, PCNs) or a small interfering RNA to silence IL-10 (IL-10 small interfering RNA-encapsulated PLGA NPs, PINs). Treatment of BMDCs with both types of PLGA NPs increased the Th1/Th2 cytokine (IL-12/IL-10) expression ratio, which is important for the effective induction of an antitumor immune response. After primary injection with the HA/PTX complex, the tumor-associated antigen was generated and taken up by tumor-recruited BMDCs. After a secondary injection with immunomodulating PCNs and PINs, the BMDCs became activated and migrated to the tumor-draining lymph nodes. As a result, the combination of chemotherapy using the HA/PTX complex and immunotherapy using PCNs and PINs not only efficiently inhibited tumor growth but also increased the animal survival rate. Taken together, our results suggest that the sequential treatment of cancer cells with a chemotherapeutic agent and immunomodulatory nanomaterials represents a promising strategy for efficient cancer therapy. Keywords: nanoparticles, chemoimmunotherapy, dendritic cells, cancer, siRNA
format	article
author	Heo MB Kim SY Yun WS Lim YT
author_facet	Heo MB Kim SY Yun WS Lim YT
author_sort	Heo MB
title	Sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy
title_short	Sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy
title_full	Sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy
title_fullStr	Sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy
title_full_unstemmed	Sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy
title_sort	sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/d65312e1aa5a403197423da01c26a875
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_version_	1718399368574271488

Sequential delivery of an anticancer drug and combined immunomodulatory nanoparticles for efficient chemoimmunotherapy

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