Modified PAMAM vehicles for effective TRAIL gene delivery to colon adenocarcinoma:<i>in vitro</i>and<i>in vivo</i>evaluation

Pishavar, Elham; Attaranzadeh, Armin; Alibolandi, Mona; Ramezani, Mohammad; Hashemi, Maryam

doi:10.1080/21691401.2018.1500372

Cited by 32 publications

(19 citation statements)

References 38 publications

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“…It is also reported that Wnt signaling in tumor cells is inhibited by chemerin while nexin is a downstream target of Wnt signaling [43][44][45]. We also observed that the levels of p53 and TRAIL were elevated by dopamine and reduced by cholesterol, in which p53 is a well-known tumor suppressor [46], and TRAIL is an apoptosis inducer of tumor cells [47]. Taken together, this study indicates that the upregulation of chemerin, TRAIL, and p53 as well as the downregulation of nexin by mechanical loading contributes to Lrp5-dependent and independent mechanisms by downregulating Lrp5, MMP2, MMP3, MMP9, Runx2, Snail, and TGFβ in tumor cells.…”

Section: Discussionsupporting

confidence: 65%

Mechanical Loading-Driven Tumor Suppression Is Mediated by Lrp5-Dependent and Independent Mechanisms

Yuan

Liu

Zha

et al. 2021

Cancers

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Bone is mechanosensitive and lipoprotein receptor-related protein 5 (Lrp5)-mediated Wnt signaling promotes loading-driven bone formation. While mechanical loading can suppress tumor growth, the question is whether Lrp5 mediates loading-driven tumor suppression. Herein, we examined the effect of Lrp5 using osteocyte-specific Lrp5 conditional knockout mice. All mice presented noticeable loading-driven tumor suppression in the loaded tibia and non-loaded mammary pad. The degree of suppression was more significant in wild-type than knockout mice. In all male and female mice, knee loading reduced cholesterol and elevated dopamine. It reduced tumor-promoting nexin, which was elevated by cholesterol and reduced by dopamine. By contrast, it elevated p53, TNF-related apoptosis-inducing ligand (TRAIL), and chemerin, and they were regulated reversely by dopamine and cholesterol. Notably, Lrp5 overexpression in osteocytes enhanced tumor suppression, and osteoclast development was inhibited by chemerin. Collectively, this study identified Lrp5-dependent and independent mechanisms for tumor suppression. Lrp5 in osteocytes contributed to the loaded bone, while the Lrp5-independent regulation of dopamine- and cholesterol-induced systemic suppression.

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Section: Discussionsupporting

confidence: 65%

Mechanical Loading-Driven Tumor Suppression Is Mediated by Lrp5-Dependent and Independent Mechanisms

Yuan

Liu

Zha

et al. 2021

Cancers

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“…Furthermore, in vivo studies demonstrated that G5-DAT66/pTRAIL efficiently inhibited tumor growth in osteosarcoma-bearing mice. Pishavar et al synthesized a vector composed of PAMAM dendrimers modified with alkyl-carboxylate chains, PEG, and cholesteryl chloroformate for delivering pTRAIL, and these PAMAM G4-alkyl-PEG (3%)-Chol (5%)-TRAIL complexes inhibited CT26 tumor growth in mice [67].…”

Section: Nonviral Vectorsmentioning

confidence: 99%

TRAIL-based gene delivery and therapeutic strategies

Zhong

Wang

et al. 2019

Acta Pharmacol Sin

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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.

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“…Genetic mutations in specific genes increase the risk of developing the disease [25]. Gene delivery systems have been widely applied to develop gene therapy classified to viral and nonviral vectors [26]. Local delivery to the retina can increase half-life therapeutic agents and reduce immune reactions, while direct retinal gene/drug delivery is a remarkably invasive procedure [27].…”

Section: Novel Drug Delivery Systemsmentioning

confidence: 99%

Nanocarriers, Progenitor Cells, Combinational Approaches, and New Insights on the Retinal Therapy

Pishavar

Luo

Bolander

et al. 2021

IJMS

Self Cite

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Progenitor cells derived from the retinal pigment epithelium (RPECs) have shown promise as therapeutic approaches to degenerative retinal disorders including diabetic retinopathy, age-related macular degeneration and Stargardt disease. However, the degeneration of Bruch’s membrane (BM), the natural substrate for the RPE, has been identified as one of the major limitations for utilizing RPECs. This degeneration leads to decreased support, survival and integration of the transplanted RPECs. It has been proposed that the generation of organized structures of nanofibers, in an attempt to mimic the natural retinal extracellular matrix (ECM) and its unique characteristics, could be utilized to overcome these limitations. Furthermore, nanoparticles could be incorporated to provide a platform for improved drug delivery and sustained release of molecules over several months to years. In addition, the incorporation of tissue-specific genes and stem cells into the nanostructures increased the stability and enhanced transfection efficiency of gene/drug to the posterior segment of the eye. This review discusses available drug delivery systems and combination therapies together with challenges associated with each approach. As the last step, we discuss the application of nanofibrous scaffolds for the implantation of RPE progenitor cells with the aim to enhance cell adhesion and support a functionally polarized RPE monolayer.

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Modified PAMAM vehicles for effective TRAIL gene delivery to colon adenocarcinoma:in vitroandin vivoevaluation

Cited by 32 publications

References 38 publications

Mechanical Loading-Driven Tumor Suppression Is Mediated by Lrp5-Dependent and Independent Mechanisms

Mechanical Loading-Driven Tumor Suppression Is Mediated by Lrp5-Dependent and Independent Mechanisms

TRAIL-based gene delivery and therapeutic strategies

Nanocarriers, Progenitor Cells, Combinational Approaches, and New Insights on the Retinal Therapy

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