Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer

Abstract The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and degradation of the chemodrug hamper the efficacy and effectiveness of intravesical chemotherapy following tumor resection. Herein, t...

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Main Authors: Cheng‐Che Chen, Yu‐Chen Fa, Yen‐Yu Kuo, Yi‐Chun Liu, Chih‐Yu Lin, Xin‐Hui Wang, Yu‐Huan Lu, Yu‐Han Chiang, Chia‐Min Yang, Li‐Chen Wu, Ja‐an Annie Ho
Format: Article
Language:English
Published: Wiley 2023-03-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202204643
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author Cheng‐Che Chen
Yu‐Chen Fa
Yen‐Yu Kuo
Yi‐Chun Liu
Chih‐Yu Lin
Xin‐Hui Wang
Yu‐Huan Lu
Yu‐Han Chiang
Chia‐Min Yang
Li‐Chen Wu
Ja‐an Annie Ho
author_facet Cheng‐Che Chen
Yu‐Chen Fa
Yen‐Yu Kuo
Yi‐Chun Liu
Chih‐Yu Lin
Xin‐Hui Wang
Yu‐Huan Lu
Yu‐Han Chiang
Chia‐Min Yang
Li‐Chen Wu
Ja‐an Annie Ho
author_sort Cheng‐Che Chen
collection DOAJ
description Abstract The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and degradation of the chemodrug hamper the efficacy and effectiveness of intravesical chemotherapy following tumor resection. Herein, the externally thiolated hollow mesoporous silica nanoparticles (MSN‐SH(E)) is fabricated to serve as a platform for improved bladder intravesical therapy. Enhanced mucoadhesive effect of the thiolated nanovector is confirmed with porcine bladder. The permeation‐enhancing effect is also verified, and a fragmented distribution pattern of a tight junction protein, claudin‐4, indicates the opening of tight junction. Moreover, MSN‐SH(E)‐associated reprogramming of M2 macrophages to M1‐like phenotype is observed in vitro. The antitumor activity of the mitomycin C (MMC)‐loaded nanovector (MMC@MSN‐SH(E)) is more effective than that of MMC alone in both in vitro and in vivo. In addition, IHC staining is used to analyze IFN‐γ, TGF‐β1, and TNF‐α. These observations substantiated the significance of MMC@MSN‐SH(E) in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non‐muscle invasive bladder cancer (NMIBC) due to its mucoadhesivity, enhanced permeation, immunomodulation, and prolonged and very efficient drug exposure.
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spelling doaj.art-7ebdc28946794ac78b9603c8ddf122ec2023-03-03T08:59:14ZengWileyAdvanced Science2198-38442023-03-01107n/an/a10.1002/advs.202204643Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder CancerCheng‐Che Chen0Yu‐Chen Fa1Yen‐Yu Kuo2Yi‐Chun Liu3Chih‐Yu Lin4Xin‐Hui Wang5Yu‐Huan Lu6Yu‐Han Chiang7Chia‐Min Yang8Li‐Chen Wu9Ja‐an Annie Ho10BioAnalytical Chemistry and Nanobiomedicine Laboratory Department of Biochemical Science and Technology National Taiwan University 10617 Taipei TaiwanBioAnalytical Chemistry and Nanobiomedicine Laboratory Department of Biochemical Science and Technology National Taiwan University 10617 Taipei TaiwanDepartment of Chemistry National Tsing Hua University 300044 Hsinchu TaiwanBioAnalytical Chemistry and Nanobiomedicine Laboratory Department of Biochemical Science and Technology National Taiwan University 10617 Taipei TaiwanDepartment of Chemistry National Tsing Hua University 300044 Hsinchu TaiwanInstrumentation Center National Taiwan University 10617 Taipei TaiwanDepartment of Chemistry National Tsing Hua University 300044 Hsinchu TaiwanDepartment of Chemistry National Taiwan University 10617 Taipei TaiwanDepartment of Chemistry National Tsing Hua University 300044 Hsinchu TaiwanDepartment of Applied Chemistry National Chi Nan University Puli Nantou 54561 TaiwanBioAnalytical Chemistry and Nanobiomedicine Laboratory Department of Biochemical Science and Technology National Taiwan University 10617 Taipei TaiwanAbstract The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and degradation of the chemodrug hamper the efficacy and effectiveness of intravesical chemotherapy following tumor resection. Herein, the externally thiolated hollow mesoporous silica nanoparticles (MSN‐SH(E)) is fabricated to serve as a platform for improved bladder intravesical therapy. Enhanced mucoadhesive effect of the thiolated nanovector is confirmed with porcine bladder. The permeation‐enhancing effect is also verified, and a fragmented distribution pattern of a tight junction protein, claudin‐4, indicates the opening of tight junction. Moreover, MSN‐SH(E)‐associated reprogramming of M2 macrophages to M1‐like phenotype is observed in vitro. The antitumor activity of the mitomycin C (MMC)‐loaded nanovector (MMC@MSN‐SH(E)) is more effective than that of MMC alone in both in vitro and in vivo. In addition, IHC staining is used to analyze IFN‐γ, TGF‐β1, and TNF‐α. These observations substantiated the significance of MMC@MSN‐SH(E) in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non‐muscle invasive bladder cancer (NMIBC) due to its mucoadhesivity, enhanced permeation, immunomodulation, and prolonged and very efficient drug exposure.https://doi.org/10.1002/advs.202204643bladder cancerintravesical therapymesoporous silica nanoparticlemitomycin Cthiol modification
spellingShingle Cheng‐Che Chen
Yu‐Chen Fa
Yen‐Yu Kuo
Yi‐Chun Liu
Chih‐Yu Lin
Xin‐Hui Wang
Yu‐Huan Lu
Yu‐Han Chiang
Chia‐Min Yang
Li‐Chen Wu
Ja‐an Annie Ho
Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer
Advanced Science
bladder cancer
intravesical therapy
mesoporous silica nanoparticle
mitomycin C
thiol modification
title Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer
title_full Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer
title_fullStr Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer
title_full_unstemmed Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer
title_short Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer
title_sort thiolated mesoporous silica nanoparticles as an immunoadjuvant to enhance efficacy of intravesical chemotherapy for bladder cancer
topic bladder cancer
intravesical therapy
mesoporous silica nanoparticle
mitomycin C
thiol modification
url https://doi.org/10.1002/advs.202204643
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