New path to treating pancreatic cancer: TRAIL gene delivery targeting the fibroblast-enriched tumor microenvironment

Jiang, Haiping; Wang, Sujuan; Zhou, Xuefei; Wang, Liying; Ye, Lidan; Zhou, Zhuxian; Tang, Jianbin; Liu, Xiangrui; Teng, Lisong; Shen, Youqing

doi:10.1016/j.jconrel.2018.07.047

Cited by 32 publications

(15 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, a γ-PGA corona can shield the positive charge of the PEI/DNA complex, thereby decreasing its toxicity and increasing its stability. It has been reported that the γ-PGA-coated branched PEI/pTRAIL complex can efficiently transfect pancreatic stellate cells expressing fibroblast growth factor receptors [48].…”

Section: Nonviral Vectorsmentioning

confidence: 99%

TRAIL-based gene delivery and therapeutic strategies

Zhong

Wang

et al. 2019

Acta Pharmacol Sin

View full text Add to dashboard Cite

TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), also known as APO2L, belongs to the tumor necrosis factor family. By binding to the death receptor 4 (DR4) or DR5, TRAIL induces apoptosis of tumor cells without causing side toxicity in normal tissues. In recent years TRAIL-based therapy has attracted great attention for its promise of serving as a cancer drug candidate. However, the treatment efficacy of TRAIL protein was under expectation in the clinical trials because of the short half-life and the resistance of cancer cells. TRAIL gene transfection can produce a "bystander effect" of tumor cell killing and provide a potential solution to TRAIL-based cancer therapy. In this review we focus on TRAIL gene therapy and various design strategies of TRAIL DNA delivery including non-viral vectors and cell-based TRAIL therapy. In order to sensitize the tumor cells to TRAIL-induced apoptosis, combination therapy of TRAIL DNA with other drugs by the codelivery methods for yielding a synergistic antitumor efficacy is summarized. The opportunities and challenges of TRAIL-based gene delivery and therapy are discussed.

show abstract

Section: Nonviral Vectorsmentioning

confidence: 99%

TRAIL-based gene delivery and therapeutic strategies

Zhong

Wang

et al. 2019

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…[ 12 ] To investigate and clarify the universality of our findings, we repeated the experiments on a new pair of cancerous and healthy pancreas cells. We chose pancreas cancer cells (PANC‐1 cells) because they use macropinocytosis, [ 39 ] and clathrin‐mediated endocytosis [ 40 ] as the dominant pathways, which is similar to MCF7 cells. We chose (non‐tumourigenic) patient‐derived cancer‐associated fibroblasts (CAFs) to compare with pancreatic cancer PANC‐1 cells.…”

Section: Resultsmentioning

confidence: 99%

Can the Shape of Nanoparticles Enable the Targeting to Cancer Cells over Healthy Cells?

Cong

Wang

Tilley

et al. 2021

Adv Funct Materials

View full text Add to dashboard Cite

Macropinocytosis is a consequence of oncogenic alterations of cancer cells while most healthy cells are non‐macropinocytic. It is currently unclear whether macropinocytic cancer cells can be targeted rather than healthy cells, by adjusting the shape and size of nanoparticles. Herein, the endocytosis of two differently shaped nanoparticles; nanorods and nanospheres are compared in cancer and healthy cells. The cells are breast epithelial cancer cells (MCF7) and breast epithelial healthy cells (MCF10A) and pancreas cancer cells (PANC‐1 cells) and non‐tumourogenic patient‐derived cancer‐associated fibroblasts (CAFs). The endocytosis pathway is quantified by a combination of pair correlation microscopy and endocytosis inhibitors. MCF7 cells use clathrin‐mediated endocytosis and macropinocytosis to take up the nanorods while MCF10A cells use predominantly clathrin‐mediated endocytosis. Based on the comparison of endocytic behavior of cancer and healthy cells, MCF7 cells can be induced to take up more nanorods and suppress the metabolism and endocytosis of nanorods in MCF10A cells. The nanorods allow targeting to breast cancer MCF7 cells and pancreas cancer cells over the healthy cells. This study opens exciting possibilities for shape to target the cancer cells over healthy cells, by adjusting nanoparticle shape.

show abstract

“…Despite this ability being traditionally considered exclusive of viruses, by either modifying composition of complexes [159] or of carrier biomaterials [160][161][162][163], it is possible to selectively transfect certain cell types [1]. With respect to modifications on DNA complexes, conjugation with HA facilitated transfection of cells overexpressing the CD44 [28], conjugation of niosomes with transferrin allowed their internalised by transferrin receptor-mediated endocytosis [164], whilst coating of DNA polyplexes with poly-γ glutamic acid (γ-PGA) allowed specific binding to the tumour-associated gamma-glutamyl transpeptidase (GGT) [165]. DNA nanoplexes containing heparin or folic acid PEI derivatives in vitro led to higher transfection efficiency and lower toxicity compared to unmodified PEI [166].…”

Section: Ecm Cuesmentioning

confidence: 99%

Physical and mechanical cues affecting biomaterial-mediated plasmid DNA delivery: insights into non-viral delivery systems

Graceffa

2021

Journal of Genetic Engineering and Biotechnology

View full text Add to dashboard Cite

Background Whilst traditional strategies to increase transfection efficiency of non-viral systems aimed at modifying the vector or the polyplexes/lipoplexes, biomaterial-mediated gene delivery has recently sparked increased interest. This review aims at discussing biomaterial properties and unravelling underlying mechanisms of action, for biomaterial-mediated gene delivery. DNA internalisation and cytoplasmic transport are initially discussed. DNA immobilisation, encapsulation and surface-mediated gene delivery (SMD), the role of extracellular matrix (ECM) and topographical cues, biomaterial stiffness and mechanical stimulation are finally outlined. Main text Endocytic pathways and mechanisms to escape the lysosomal network are highly variable. They depend on cell and DNA complex types but can be diverted using appropriate biomaterials. 3D scaffolds are generally fabricated via DNA immobilisation or encapsulation. Degradation rate and interaction with the vector affect temporal patterns of DNA release and transgene expression. In SMD, DNA is instead coated on 2D surfaces. SMD allows the incorporation of topographical cues, which, by inducing cytoskeletal re-arrangements, modulate DNA endocytosis. Incorporation of ECM mimetics allows cell type-specific transfection, whereas in spite of discordances in terms of optimal loading regimens, it is recognised that mechanical loading facilitates gene transfection. Finally, stiffer 2D substrates enhance DNA internalisation, whereas in 3D scaffolds, the role of stiffness is still dubious. Conclusion Although it is recognised that biomaterials allow the creation of tailored non-viral gene delivery systems, there still are many outstanding questions. A better characterisation of endocytic pathways would allow the diversion of cell adhesion processes and cytoskeletal dynamics, in order to increase cellular transfection. Further research on optimal biomaterial mechanical properties, cell ligand density and loading regimens is limited by the fact that such parameters influence a plethora of other different processes (e.g. cellular adhesion, spreading, migration, infiltration, and proliferation, DNA diffusion and release) which may in turn modulate gene delivery. Only a better understanding of these processes may allow the creation of novel robust engineered systems, potentially opening up a whole new area of biomaterial-guided gene delivery for non-viral systems.

show abstract

New path to treating pancreatic cancer: TRAIL gene delivery targeting the fibroblast-enriched tumor microenvironment

Cited by 32 publications

References 39 publications

TRAIL-based gene delivery and therapeutic strategies

TRAIL-based gene delivery and therapeutic strategies

Can the Shape of Nanoparticles Enable the Targeting to Cancer Cells over Healthy Cells?

Physical and mechanical cues affecting biomaterial-mediated plasmid DNA delivery: insights into non-viral delivery systems

Contact Info

Product

Resources

About