Reversal of pancreatic desmoplasia by a tumour stroma-targeted nitric oxide nanogel overcomes TRAIL resistance in pancreatic tumours

Huang, Hsi‐Chien; Sung, Yun‐Chieh; Li, Chung–Pin; Wan, Dehui; Chao, Po-Han; Tseng, Yu‐Ting; Liao, Bo-Wen; Cheng, Hongyan; Hsu, Fu-Fei; Huang, Chieh‐Cheng; Chen, Yi-Ting; Liao, Yuhui; Hsieh, Hsin Tzu; Shih, Yu‐Chuan; Liu, I-Ju; Wu, Han‐Chung; Lu, Tsai‐Te; Wang, Jane

doi:10.1136/gutjnl-2021-325180

Cited by 22 publications

(11 citation statements)

References 43 publications

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“…Hydrogel is an extremely hydrophilic polymer material with a three-dimensional network structure [ 1 ]. As an excellent water absorption and water retention material, hydrogel has attracted considerable attention in the past few years and has been widely used in the fields of food [ 2 , 3 ], cosmetics [ 4 ], tissue engineering [ 5 ], and drug delivery [ 6 ] as a typical natural polymer.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Properties of Salecan–Soy Protein Isolate Composite Hydrogel Induced by Thermal Treatment and Transglutaminase

Gan

Sun

Guan

et al. 2022

IJMS

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Salecan (Sal) is a novel marine microbial polysaccharide. In the present research, Sal and soy protein isolate (SPI) were adopted to fabricate Sal–SPI composite hydrogel based on a stepwise process (thermal treatment and transglutaminase induction). The effect of Sal concentration on morphology, texture properties, and the microstructure of the hydrogel was evaluated. As Sal concentration varied from 0.4 to 0.6 wt%, hydrogel elasticity increased from 0.49 to 0.85 mm. Furthermore, the internal network structure of Sal–SPI composite hydrogel also became denser and more uniform as Sal concentration increased. Rheological studies showed that Sal–SPI elastic hydrogel formed under the gelation process. Additionally, FTIR and XRD results demonstrated that hydrogen bonds formed between Sal and SPI molecules, inferring the formation of the interpenetrating network structure. This research supplied a green and simple method to fabricate Sal–SPI double network hydrogels.

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Section: Introductionmentioning

confidence: 99%

Preparation and Properties of Salecan–Soy Protein Isolate Composite Hydrogel Induced by Thermal Treatment and Transglutaminase

Gan

Sun

Guan

et al. 2022

IJMS

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“…The delivery of NO to the PDAC tumor stroma resulted in the reprogramming of activated pancreatic stellate cells, alleviation of tumor desmoplasia, and suppression of antiapoptotic Bcl-2 protein expression, resulting in facilitated tumor penetration by TRAIL and enhanced TRAIL antitumor efficacy in three-dimensional spheroid cultures in vitro and in orthotopic PDAC models in vivo. Thus, the co-delivery of TRAIL and NO by a stroma-targeted nanogel that remodels the fibrotic tumor microenvironment and suppresses tumor growth is promising for PDAC treatment [ 89 ].…”

Section: Polymer-based Systems For Nanodelivery Of Trail Pathway-targ...mentioning

confidence: 99%

“…ECM, extracellular matrix; NO, nitric oxide; NPs, nanoparticle; PDAC, pancreatic ductal adenocarcinoma; PSC, pancreatic stellate cells; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand. Reproduced with permission from [ 89 ]. Copyright © 2022, BMJ Publishing Group Ltd. & British Society of Gastroenterology (CC BY-NC 4.0 (accessed on 20 January 2023)).…”

Section: Figurementioning

confidence: 99%

Recent Advances in the Development of Nanodelivery Systems Targeting the TRAIL Death Receptor Pathway

2023

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The TRAIL (TNF-related apoptosis-inducing ligand) apoptotic pathway is extensively exploited in the development of targeted antitumor therapy due to TRAIL specificity towards its cognate receptors, namely death receptors DR4 and DR5. Although therapies targeting the TRAIL pathway have encountered many obstacles in attempts at clinical implementation for cancer treatment, the unique features of the TRAIL signaling pathway continue to attract the attention of researchers. Special attention is paid to the design of novel nanoscaled delivery systems, primarily aimed at increasing the valency of the ligand for improved death receptor clustering that enhances apoptotic signaling. Optionally, complex nanoformulations can allow the encapsulation of several therapeutic molecules for a combined synergistic effect, for example, chemotherapeutic agents or photosensitizers. Scaffolds for the developed nanodelivery systems are fabricated by a wide range of conventional clinically approved materials and innovative ones, including metals, carbon, lipids, polymers, nanogels, protein nanocages, virus-based nanoparticles, dendrimers, DNA origami nanostructures, and their complex combinations. Most nanotherapeutics targeting the TRAIL pathway are aimed at tumor therapy and theranostics. However, given the wide spectrum of action of TRAIL due to its natural role in immune system homeostasis, other therapeutic areas are also involved, such as liver fibrosis, rheumatoid arthritis, Alzheimer’s disease, and inflammatory diseases caused by bacterial infections. This review summarizes the recent innovative developments in the design of nanodelivery systems modified with TRAIL pathway-targeting ligands.

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“…A PEGylated human recombinant TRAIL named TLY012 ameliorated skin fibrosis, pancreatic disease and cirrhosis in preclinical models [ 211 ] and is being actively investigated for anticancer effects in tumor models but is yet to be tested in TNBC models [ 212 ]. Recently, a nanogel delivering nitric oxide and TRAIL to pancreatic ductal adeno carcinoma xenografts had enhanced tumor penetration and efficacy [ 213 ]. A paclitaxel (PTX)-bound albumin nanoparticles with embedded TRAIL (TRAIL/PTX HSA-NP) formulation based on paclitaxel-bound albumin nanoparticles embedded with TRAIL showed improved TRAIL efficacy both in vitro and in vivo pancreatic cancer models [ 214 ].…”

Section: Strategies To Improve Dr Agonists In Patients With Breast Ca...mentioning

confidence: 99%

Targeting TRAIL Death Receptors in Triple-Negative Breast Cancers: Challenges and Strategies for Cancer Therapy

Kundu

Greer

Dine

et al. 2022

Cells

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The tumor necrosis factor (TNF) superfamily member TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells via death receptor (DR) activation with little toxicity to normal cells or tissues. The selectivity for activating apoptosis in cancer cells confers an ideal therapeutic characteristic to TRAIL, which has led to the development and clinical testing of many DR agonists. However, TRAIL/DR targeting therapies have been widely ineffective in clinical trials of various malignancies for reasons that remain poorly understood. Triple negative breast cancer (TNBC) has the worst prognosis among breast cancers. Targeting the TRAIL DR pathway has shown notable efficacy in a subset of TNBC in preclinical models but again has not shown appreciable activity in clinical trials. In this review, we will discuss the signaling components and mechanisms governing TRAIL pathway activation and clinical trial findings discussed with a focus on TNBC. Challenges and potential solutions for using DR agonists in the clinic are also discussed, including consideration of the pharmacokinetic and pharmacodynamic properties of DR agonists, patient selection by predictive biomarkers, and potential combination therapies. Moreover, recent findings on the impact of TRAIL treatment on the immune response, as well as novel strategies to address those challenges, are discussed.

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Reversal of pancreatic desmoplasia by a tumour stroma-targeted nitric oxide nanogel overcomes TRAIL resistance in pancreatic tumours

Cited by 22 publications

References 43 publications

Preparation and Properties of Salecan–Soy Protein Isolate Composite Hydrogel Induced by Thermal Treatment and Transglutaminase

Preparation and Properties of Salecan–Soy Protein Isolate Composite Hydrogel Induced by Thermal Treatment and Transglutaminase

Recent Advances in the Development of Nanodelivery Systems Targeting the TRAIL Death Receptor Pathway

Targeting TRAIL Death Receptors in Triple-Negative Breast Cancers: Challenges and Strategies for Cancer Therapy

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