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纳米肿瘤坏死因子相关凋亡诱导配体：癌症治疗的一条充满希望的途径。

Nano-TRAIL: a promising path to cancer therapy.

作者信息

Gampa Siri Chandana, Garimella Sireesha V, Pandrangi SanthiLatha

机构信息

Department of Biotechnology, Institute of Science, GITAM (Deemed to be University), Andhra Pradesh 530045, India.

Department of Biochemistry and Bioinformatics, Institute of Science, GITAM (Deemed to be University), Andhra Pradesh 530045, India.

出版信息

Cancer Drug Resist. 2023 Feb 1;6(1):78-102. doi: 10.20517/cdr.2022.82. eCollection 2023.

DOI:10.20517/cdr.2022.82
PMID:37065863
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10099604/
Abstract

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand, also called apo-2 ligand (TRAIL/Apo-2L), is a cytokine that triggers apoptosis by binding to TRAIL-R1 (DR4) and TRAIL-R2 (DR5) death receptors. Apoptosis occurs through either the extrinsic or intrinsic pathway. The administration of recombinant human TRAIL (rhTRAIL) or TRAIL-receptor (TRAIL-R) agonists promotes apoptosis preferentially in cancerous cells over normal cells ; this phenomenon has also been observed in clinical studies. The limited efficacy of rhTRAIL in clinical trials could be attributed to drug resistance, short half-life, targeted delivery issues, and off-target toxicities. Nanoparticles are excellent drug and gene delivery systems characterized by improved permeability and retention, increased stability and biocompatibility, and precision targeting. In this review, we discuss resistance mechanisms to TRAIL and methods to overcome TRAIL resistance by using nanoparticle-based formulations developed for the delivery of TRAIL peptides, TRAIL-R agonists, and TRAIL genes to cancer cells. We also discuss combinatorial approaches of chemotherapeutic drugs with TRAIL. These studies demonstrate TRAIL's potential as an anticancer agent.

摘要

肿瘤坏死因子相关凋亡诱导配体，也称为载脂蛋白2配体（TRAIL/Apo-2L），是一种细胞因子，通过与TRAIL-R1（DR4）和TRAIL-R2（DR5）死亡受体结合触发细胞凋亡。细胞凋亡通过外源性或内源性途径发生。重组人TRAIL（rhTRAIL）或TRAIL受体（TRAIL-R）激动剂的给药在癌细胞中比在正常细胞中更优先地促进细胞凋亡；这种现象在临床研究中也已观察到。rhTRAIL在临床试验中的疗效有限可能归因于耐药性、半衰期短、靶向递送问题和脱靶毒性。纳米颗粒是优异的药物和基因递送系统，其特征在于改善的通透性和滞留性、增加的稳定性和生物相容性以及精确靶向性。在本综述中，我们讨论了对TRAIL的耐药机制以及通过使用为将TRAIL肽、TRAIL-R激动剂和TRAIL基因递送至癌细胞而开发的基于纳米颗粒的制剂来克服TRAIL耐药性的方法。我们还讨论了化疗药物与TRAIL的联合应用方法。这些研究证明了TRAIL作为抗癌剂的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cd6/10099604/fe390a1c4de0/cdr-6-1-78.fig.4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cd6/10099604/e49604d797e5/cdr-6-1-78.fig.1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cd6/10099604/a361f900030e/cdr-6-1-78.fig.2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cd6/10099604/a8c0e617c07e/cdr-6-1-78.fig.3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cd6/10099604/fe390a1c4de0/cdr-6-1-78.fig.4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cd6/10099604/e49604d797e5/cdr-6-1-78.fig.1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cd6/10099604/a361f900030e/cdr-6-1-78.fig.2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cd6/10099604/a8c0e617c07e/cdr-6-1-78.fig.3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cd6/10099604/fe390a1c4de0/cdr-6-1-78.fig.4.jpg

相似文献

[1]
Nano-TRAIL: a promising path to cancer therapy.

Cancer Drug Resist. 2023-2-1

[2]
Pretreatment with paclitaxel enhances apo-2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of prostate cancer cells by inducing death receptors 4 and 5 protein levels.

Cancer Res. 2001-1-15

[3]
Tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in established and primary glioma cell lines.

Neurosurg Focus. 2002-9-15

[4]
Cotreatment with STI-571 enhances tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL or apo-2L)-induced apoptosis of Bcr-Abl-positive human acute leukemia cells.

Clin Cancer Res. 2001-2

[5]
DR4 specific TRAIL variants are more efficacious than wild-type TRAIL in pancreatic cancer.

Cancer Biol Ther. 2014

[6]
Enhancement of therapeutic potential of TRAIL by cancer chemotherapy and irradiation: mechanisms and clinical implications.

Drug Resist Updat. 2004-4

[7]
Should We Keep Walking along the Trail for Pancreatic Cancer Treatment? Revisiting TNF-Related Apoptosis-Inducing Ligand for Anticancer Therapy.

Cancers (Basel). 2018-3-18

[8]
The TRAIL to cancer therapy: Hindrances and potential solutions.

Crit Rev Oncol Hematol. 2019-9-8

[9]
Effects of sequential treatments with chemotherapeutic drugs followed by TRAIL on prostate cancer in vitro and in vivo.

Prostate. 2005-2-1

[10]
TRAILblazing Strategies for Cancer Treatment.

Cancers (Basel). 2019-3-30

引用本文的文献

[1]
Turn TRAIL Into Better Anticancer Therapeutic Through TRAIL Fusion Proteins.

Cancer Med. 2025-1

[2]
Targeting Death Receptor 5 (DR5) for the imaging and treatment of primary bone and soft tissue tumors: an update of the literature.

Front Mol Biosci. 2024-9-2

[3]
Nanoparticle-mediated gene delivery of TRAIL to resistant cancer cells: A review.

Heliyon. 2024-8-8

[4]
Cell death pathways: molecular mechanisms and therapeutic targets for cancer.

MedComm (2020). 2024-9-4

[5]
Targeting the Molecules in EMT: A Potential Therapeutic Opportunity in Breast Cancer.

Curr Mol Med. 2025

[6]
Circular RNA in cervical cancer: Fundamental mechanism and clinical potential.

Noncoding RNA Res. 2023-11-18

[7]
Mitochondria in Cancer Stem Cells: From an Innocent Bystander to a Central Player in Therapy Resistance.

Stem Cells Cloning. 2023-8-23

本文引用的文献

[1]
TRAIL & EGFR affibody dual-display on a protein nanoparticle synergistically suppresses tumor growth.

J Control Release. 2022-9

[2]
Polymer Nanoparticles Overcome Drug Resistance by a Dual-Targeting Apoptotic Signaling Pathway in Breast Cancer.

ACS Appl Mater Interfaces. 2022-5-11

[3]
TRAIL/S-layer/graphene quantum dot nanohybrid enhanced stability and anticancer activity of TRAIL on colon cancer cells.

Sci Rep. 2022-4-7

[4]
Death Receptors DR4 and DR5 Undergo Spontaneous and Ligand-Mediated Endocytosis and Recycling Regardless of the Sensitivity of Cancer Cells to TRAIL.

Front Cell Dev Biol. 2021-9-30

[5]
TRAIL Conjugated Silver Nanoparticle Synthesis, Characterization and Therapeutic Effects on HT-29 Colon Cancer Cells.

Iran J Pharm Res. 2021

[6]
Poly(beta-amino ester) nanoparticles enable tumor-specific TRAIL secretion and a bystander effect to treat liver cancer.

Mol Ther Oncolytics. 2021-4-16

[7]
The TRAIL in the Treatment of Human Cancer: An Update on Clinical Trials.

Front Mol Biosci. 2021-3-10

[8]
Grafting TRAIL through Either Amino or Carboxylic Groups onto Maghemite Nanoparticles: Influence on Pro-Apoptotic Efficiency.

Nanomaterials (Basel). 2021-2-17

[9]
Revisiting the role of TRAIL/TRAIL-R in cancer biology and therapy.

Future Oncol. 2021-2

[10]
Engineering of Doxorubicin-Encapsulating and TRAIL-Conjugated Poly(RGD) Proteinoid Nanocapsules for Drug Delivery Applications.

Polymers (Basel). 2020-12-16

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