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Nanoparticle-mediated gene delivery of TRAIL to resistant cancer cells: A review
Mina Habibizadeh1, Shima Lotfollahzadeh2, Parisa Mahdavi3
1Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Abstract:
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), also known as APO2L, has emerged as a highly potential anticancer agent because of its capacity to effectively trigger apoptosis in tumor cells by specifically binding to either of its death receptors (DR4 or DR5) while having no adverse effects on normal cells. Nevertheless, its practical use has been hindered by its inefficient pharmacokinetics characteristics, the challenges involved in its administration and delivery to targeted cells, and the resistance exhibited by most cancer cells towards TRAIL. Gene therapy, as a promising approach would be able to potentially circumvent TRAIL-based cancer therapy challenges mainly through localized TRAIL expression and generating a bystander impact. Among different strategies, using nanoparticles in TRAIL gene delivery allows for precise targeting, and overcoming TRAIL resistance by combination therapy. In this review, we go over potential mechanisms by which cancer cells achieve resistance to TRAIL and provide an overview of different carriers for delivering of the TRAIL gene to resistant cancer cells, focusing on different types of nanoparticles utilized in this context. We will also explore the challenges, and investigate future perspectives of this nanomedicine approach for cancer therapy.
Insights
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows promise for cancer therapy by inducing apoptosis. Nanoparticle-based gene delivery offers a strategy to overcome challenges like poor pharmacokinetics and cancer cell resistance to TRAIL.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Cancer Research
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/APO2L) induces cancer cell apoptosis via death receptors DR4/DR5.
- Clinical application of TRAIL is limited by poor pharmacokinetics, delivery challenges, and cancer cell resistance.
Purpose of the Study:
- To review mechanisms of TRAIL resistance in cancer cells.
- To explore nanoparticle-based gene delivery systems for overcoming TRAIL resistance.
- To discuss challenges and future perspectives of nanomedicine for TRAIL gene therapy.
Main Methods:
- Literature review of TRAIL mechanisms, resistance pathways, and gene delivery strategies.
- Focus on nanoparticle carriers for TRAIL gene delivery to resistant cancer cells.
- Analysis of current challenges and future directions in nanomedicine for cancer therapy.
Main Results:
- Cancer cells develop resistance to TRAIL through various mechanisms.
- Nanoparticles offer precise targeting and potential for combination therapy to overcome TRAIL resistance.
- Gene therapy with localized TRAIL expression can create a bystander effect.
Conclusions:
- Nanoparticle-mediated TRAIL gene delivery is a promising strategy to enhance cancer therapy efficacy.
- Addressing TRAIL resistance and optimizing delivery are key for clinical translation.
- Further research into nanomedicine approaches holds significant potential for future cancer treatment.
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