A polyethylenimine-modified carboxyl-poly(styrene/acrylamide) copolymer nanosphere for co-delivering of CpG and TGF-&amp;beta; receptor I inhibitor with remarkable additive tumor regression effect against liver cancer in mice

Liang, Shuyan; Hu, Jun; Xie, Yuanyuan; Zhou, Qing; Zhu, Yanhong; Yang, Xiangliang

doi:10.2147/ijn.s122047

Cited by 13 publications

(8 citation statements)

References 44 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Galunisertib also reduced the expression of stemness-related genes, such as CD44 and THY1, in vitro and in ex vivo human HCC specimens, overcoming stemness-derived aggressiveness ( 185 ). Furthermore, it also showed antitumor activity through the activation of CD8+ T-cell antitumor responses ( 224 ). Recent studies have also suggested the potential efficiency of Galunisertib as antifibrotic drug.…”

Section: New Therapies To Inhibit the Tgf-β Pathwaymentioning

confidence: 99%

Transforming Growth Factor-β-Induced Cell Plasticity in Liver Fibrosis and Hepatocarcinogenesis

2018

View full text Add to dashboard Cite

The Transforming Growth Factor-beta (TGF-β) family plays relevant roles in the regulation of different cellular processes that are essential for tissue and organ homeostasis. In the case of the liver, TGF-β signaling participates in different stages of disease progression, from initial liver injury toward fibrosis, cirrhosis and cancer. When a chronic injury takes place, mobilization of lymphocytes and other inflammatory cells occur, thus setting the stage for persistence of an inflammatory response. Macrophages produce profibrotic mediators, among them, TGF-β, which is responsible for activation -transdifferentiation- of quiescent hepatic stellate cells (HSC) to a myofibroblast (MFB) phenotype. MFBs are the principal source of extracellular matrix protein (ECM) accumulation and prominent mediators of fibrogenesis. TGF-β also mediates an epithelial-mesenchymal transition (EMT) process in hepatocytes that may contribute, directly or indirectly, to increase the MFB population. In hepatocarcinogenesis, TGF-β plays a dual role, behaving as a suppressor factor at early stages, but contributing to later tumor progression, once cells escape from its cytostatic effects. As part of its potential pro-tumorigenic actions, TGF-β induces EMT in liver tumor cells, which increases its pro-migratory and invasive potential. In parallel, TGF-β also induces changes in tumor cell plasticity, conferring properties of a migratory tumor initiating cell (TIC). The main aim of this review is to shed light about the pleiotropic actions of TGF-β that explain its effects on the different liver cell populations. The cross-talk with other signaling pathways that contribute to TGF-β effects, in particular the Epidermal Growth Factor Receptor (EGFR), will be presented. Finally, we will discuss the rationale for targeting the TGF-β pathway in liver pathologies.

show abstract

Section: New Therapies To Inhibit the Tgf-β Pathwaymentioning

confidence: 99%

Transforming Growth Factor-β-Induced Cell Plasticity in Liver Fibrosis and Hepatocarcinogenesis

2018

View full text Add to dashboard Cite

show abstract

“…And DP-CpG treatment caused ∼46% growth inhibition, presumably because CpG motif-mediated activation of the innate immune system resulted in the inhibition of tumor growth. 65 In contrast, the control groups of saline plus laser, GT, and IR820 displayed no obvious effects of delaying the tumor growth. The dramatic inhibition efficiency mediated by GT/IR820/DP-CpG was due to the photothermal ablation of GT/IR820 and immunotherapy mediated by DP-CpG.…”

Section: ■ Results and Discussionmentioning

confidence: 95%

“…In other groups, the tumors in mice treated with GT/IR820 plus laser irradiation exhibited ∼58% growth inhibition. And DP-CpG treatment caused ∼46% growth inhibition, presumably because CpG motif-mediated activation of the innate immune system resulted in the inhibition of tumor growth . In contrast, the control groups of saline plus laser, GT, and IR820 displayed no obvious effects of delaying the tumor growth.…”

Section: Resultsmentioning

confidence: 96%

“Triple-Punch” Anticancer Strategy Mediated by Near-Infrared Photosensitizer/CpG Oligonucleotides Dual-Dressed and Mitochondria-Targeted Nanographene

Wang

Tian

et al. 2018

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Nanomedicine-based combination therapy has sparked a growing interest in clinical disease treatment and pharmaceutical industry. In this study, a mitochondria-targeted and near-infrared (NIR) light-activable multitasking nanographene (i.e., GT/IR820/DP-CpG) was engineered to in situ trigger highly efficient "triple-punch" strategy of cancer photodynamic therapy, photothermal therapy, and immunotherapy. Modification of triphenylphosphonium on graphene made the vehicle specifically guide the NIR dye IR820 home to mitochondria, followed by lysosomes escape in a time-dependent manner. The photoactive nanocomplex generated an abundant reactive oxygen species as well as photothermal heat to ultimately kill cancer cells by inducing mitochondrial collapse and irreversible cell apoptosis upon the NIR laser irradiation. Further introduction of an immunostimulatory conjugate DP-CpG significantly promoted the secretion of proinflammatory cytokines (i.e., interleukin-6, tumor necrosis factor-α, and interferon-γ) and thus improved the immunogenicity of tumors. In vivo studies demonstrated that GT/IR820/DP-CpG remarkably inhibited tumor growth (tumor inhibition rate, ∼88%) resulting from the combinational phototherapeutic effect of IR820 and immunostimulatory activity of DP-CpG, thereby causing negligible toxic effects on mice. Our work provides a new paradigm of architecting organelle-targeted and stimulative nanocomplex for highly efficient cancer photoimmunotherapy.

show abstract

“…Pei et al [108] proposed fraxinellone-loaded CGKRKmodified NPs (Frax-NP-CGKRK) to regulate TGF-β signals, resulting in the reduction of M2-TAMs and improvement of blood perfusion in the tumor sites. PEG-based core-shell nanopolyplex [110] and PEImodified carboxyl-styrene/acrylamide copolymer nanospheres [109] were developed to encapsulate the hydrophobic LY2109761, a TGF-β receptor type I kinase inhibitor, targeting the tumor stroma and then remodeling the TME (figure 6(e)). Qian et al [111] designed a zwitterionic lipid-based siTGF-β delivery nanosystem to promote endosomal/lysosomal escape, achieving enhanced gene silencing efficiency and ameliorating the immunosuppressive TME.…”

Section: Modulation Of Immunosuppressive Factors In the Tmementioning

confidence: 99%

Emerging nanotechnological strategies to reshape tumor microenvironment for enhanced therapeutic outcomes of cancer immunotherapy

Lin¹,

Wang²,

Gu³

et al. 2021

Biomed. Mater.

View full text Add to dashboard Cite

Immunotherapy has emerged as a novel cancer treatment over the last decade, however, efficacious responses to mono-immunotherapy have only been achieved in a relatively small portion of patients whereas combinational immunotherapies often lead to concurrent side effects. It has been proved that the tumor microenvironment (TME) is responsible for tumor immune escape and the ultimate treatment failure. Recently, there has been remarkable progress in both the understanding of the TME and the applications of nanotechnological strategies, and reviewing the emerging immune-regulatory nanosystems may provide valuable information for specifically modulating the TME at different immune stages. In this review, we focus on comprehending the recently-proposed T-cell-based tumor classification and identifying the most promising targets for different tumor phenotypes, and then summarizing the nanotechnological strategies to best target corresponding immune-related factors. For future precise personalized immunotherapy, tailor-made TME modulation strategies conducted by well-designed nanosystems to alleviate the suppressive TME and then promote anti-tumor immune responses will significantly benefit the clinical outcomes of cancer patients.

show abstract

A polyethylenimine-modified carboxyl-poly(styrene/acrylamide) copolymer nanosphere for co-delivering of CpG and TGF-β receptor I inhibitor with remarkable additive tumor regression effect against liver cancer in mice

Cited by 13 publications

References 44 publications

Transforming Growth Factor-β-Induced Cell Plasticity in Liver Fibrosis and Hepatocarcinogenesis

Transforming Growth Factor-β-Induced Cell Plasticity in Liver Fibrosis and Hepatocarcinogenesis

“Triple-Punch” Anticancer Strategy Mediated by Near-Infrared Photosensitizer/CpG Oligonucleotides Dual-Dressed and Mitochondria-Targeted Nanographene

Emerging nanotechnological strategies to reshape tumor microenvironment for enhanced therapeutic outcomes of cancer immunotherapy

Contact Info

Product

Resources

About