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

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 extern...

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Published inAdvanced science Vol. 10; no. 7; pp. e2204643 - n/a
Main Authors Chen, Cheng‐Che, Fa, Yu‐Chen, Kuo, Yen‐Yu, Liu, Yi‐Chun, Lin, Chih‐Yu, Wang, Xin‐Hui, Lu, Yu‐Huan, Chiang, Yu‐Han, Yang, Chia‐Min, Wu, Li‐Chen, Ho, Ja‐an Annie
Format Journal Article
LanguageEnglish
Published Germany John Wiley & Sons, Inc 01.03.2023
John Wiley and Sons Inc
Wiley
Subjects
Adjuvants, Immunologic - therapeutic use
Animals
Antibiotics, Antineoplastic
Bladder cancer
Cancer therapies
Chemotherapy
Glycoproteins
Immunotherapy
intravesical therapy
mesoporous silica nanoparticle
Mitomycin - therapeutic use
mitomycin C
Morphology
Nanoparticles
Nitrogen
Silicon Dioxide
Swine
thiol modification
Urinary Bladder Neoplasms - drug therapy
Urinary Bladder Neoplasms - pathology
Urine
mitomycin C
mesoporous silica nanoparticle
intravesical therapy
thiol modification
bladder cancer
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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. The nanovectors, mitomycin C (MMC)‐loaded, externally thiolated hollow mesoporous silica nanoparticles (MSN‐SH(E)), are confirmed to be helpful in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non‐muscle invasive bladder cancer due to its mucoadhesivity, enhanced permeation, immunomodulation and prolonged and very efficient drug exposure.
AbstractList 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. The nanovectors, mitomycin C (MMC)‐loaded, externally thiolated hollow mesoporous silica nanoparticles (MSN‐SH(E)), are confirmed to be helpful in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non‐muscle invasive bladder cancer due to its mucoadhesivity, enhanced permeation, immunomodulation and prolonged and very efficient drug exposure.
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.
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‐ β 1, 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. The nanovectors, mitomycin C (MMC)‐loaded, externally thiolated hollow mesoporous silica nanoparticles (MSN‐SH(E)), are confirmed to be helpful in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non‐muscle invasive bladder cancer due to its mucoadhesivity, enhanced permeation, immunomodulation and prolonged and very efficient drug exposure.
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.
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.
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.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.
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‐ β 1, 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.
Author Chen, Cheng‐Che
Yang, Chia‐Min
Kuo, Yen‐Yu
Lu, Yu‐Huan
Wu, Li‐Chen
Wang, Xin‐Hui
Lin, Chih‐Yu
Chiang, Yu‐Han
Ho, Ja‐an Annie
Fa, Yu‐Chen
Liu, Yi‐Chun
AuthorAffiliation 1 BioAnalytical Chemistry and Nanobiomedicine Laboratory Department of Biochemical Science and Technology National Taiwan University 10617 Taipei Taiwan
5 Department of Chemistry National Taiwan University 10617 Taipei Taiwan
7 Department of Applied Chemistry National Chi Nan University Puli Nantou 54561 Taiwan
6 Frontier Research Center on Fundamental and Applied Sciences of Matters National Tsing Hua University 300044 Hsinchu Taiwan
2 Department of Urology Taichung Veterans General Hospital 40705 Taichung Taiwan
3 Department of Chemistry National Tsing Hua University 300044 Hsinchu Taiwan
8 Center for Emerging Materials and Advance Devices National Taiwan University 10617 Taipei Taiwan
4 Instrumentation Center National Taiwan University 10617 Taipei Taiwan
9 Center for Biotechnology National Taiwan University 10617 Taipei Taiwan
AuthorAffiliation_xml – name: 2 Department of Urology Taichung Veterans General Hospital 40705 Taichung Taiwan
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– name: 5 Department of Chemistry National Taiwan University 10617 Taipei Taiwan
– name: 3 Department of Chemistry National Tsing Hua University 300044 Hsinchu Taiwan
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/36638276$$D View this record in MEDLINE/PubMed
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Issue 7
Keywords mitomycin C
mesoporous silica nanoparticle
intravesical therapy
thiol modification
bladder cancer
Language English
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2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Snippet The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and...
Abstract The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous...
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SubjectTerms Adjuvants, Immunologic - therapeutic use
Animals
Antibiotics, Antineoplastic
Bladder cancer
Cancer therapies
Chemotherapy
Glycoproteins
Immunotherapy
intravesical therapy
mesoporous silica nanoparticle
Mitomycin - therapeutic use
mitomycin C
Morphology
Nanoparticles
Nitrogen
Silicon Dioxide
Swine
thiol modification
Urinary Bladder Neoplasms - drug therapy
Urinary Bladder Neoplasms - pathology
Urine
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Title Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fadvs.202204643
https://www.ncbi.nlm.nih.gov/pubmed/36638276
https://www.proquest.com/docview/2781460847
https://www.proquest.com/docview/2765779304
https://pubmed.ncbi.nlm.nih.gov/PMC9982584
https://doaj.org/article/7ebdc28946794ac78b9603c8ddf122ec
Volume 10
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