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Nanomaterial-orchestrated PANoptosis in cancer: Molecular mechanisms, immunological crosstalk, and translational
Yuelin Zhao1, Hongyu Yang1, Siqi Wang1
1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Abstract:
The high morbidity and mortality of malignant tumors pose a severe threat to human health, and the induction of programmed cell death (PCD) in cancer cells has become a core strategy for tumor therapy. As a novel inflammatory PCD signaling network, PANoptosis integrates the core molecules and characteristic phenotypes of apoptosis, pyroptosis, and necroptosis, thereby synergistically activating these three pathways to efficiently eliminate tumor cells. However, the small-molecule compounds and cytokines used in PANoptosis research suffer from inherent drawbacks, including unsatisfactory in vivo pharmacokinetic profiles, insufficient tumor-targeted enrichment, and pronounced systemic toxic effects, which have severely hindered their clinical translation and application. Nanomaterials possess the advantages of high targeting efficiency, prolonged in vivo circulation time, and excellent physicochemical properties, providing a novel approach to break through the developmental bottlenecks of PANoptosis-inducing strategies. This review systematically elaborates on the definition, molecular mechanism, and therapeutic significance of PANoptosis in tumors, with a focus on summarizing recent advances in nanomaterial-mediated PANoptosis induction for tumor therapy. Nanomaterials can precisely trigger the assembly of PANoptosomes by activating multiple upstream sensors (e.g., ZBP1, AIM2, RIPK1, NLRP12, NLRP3/NLRC5) or inducing the simultaneous activation of multiple molecular pathways, thereby achieving efficient and targeted killing of tumor cells and remodeling the tumor microenvironment (TME). This systematic review of nanomaterials capable of triggering PANoptosis is intended to inspire innovative thinking and furnish promising therapeutic strategies for malignant tumor treatment.
Insights
Nanomaterials offer a promising strategy to enhance PANoptosis (programmed cell death) for cancer therapy. They overcome limitations of traditional methods, enabling targeted tumor cell elimination and improved treatment outcomes.
Area of Science:
- Oncology
- Immunology
- Biomedical Engineering
Background:
- Malignant tumors present significant global health challenges, driving the need for novel therapeutic strategies.
- Programmed cell death (PCD) induction is a key approach in cancer treatment.
- PANoptosis, a novel inflammatory PCD pathway, synergistically combines apoptosis, pyroptosis, and necroptosis for efficient tumor cell elimination.
Purpose of the Study:
- To review the definition, molecular mechanisms, and therapeutic potential of PANoptosis in oncology.
- To summarize recent advancements in nanomaterial-mediated PANoptosis induction for cancer therapy.
- To highlight how nanomaterials can overcome the limitations of current PANoptosis-inducing agents.
Main Methods:
- Systematic review of existing literature on PANoptosis and nanomaterial applications in cancer.
- Analysis of molecular mechanisms underlying PANoptosis induction by various sensors and pathways.
- Examination of nanomaterial properties enabling targeted delivery and enhanced therapeutic efficacy.
Main Results:
- PANoptosis integrates apoptosis, pyroptosis, and necroptosis for potent anti-cancer effects.
- Traditional PANoptosis inducers face challenges like poor pharmacokinetics and systemic toxicity.
- Nanomaterials demonstrate high targeting efficiency, prolonged circulation, and physicochemical advantages for PANoptosis induction.
- Nanomaterials can precisely trigger PANoptosome assembly via upstream sensors or pathway activation.
- Nanomaterial-mediated PANoptosis achieves targeted tumor cell killing and TME remodeling.
Conclusions:
- Nanomaterials represent a breakthrough approach for overcoming the limitations of current PANoptosis-based cancer therapies.
- Nanomaterial-mediated PANoptosis offers a promising strategy for efficient and targeted tumor elimination.
- This review provides insights for developing innovative nanomaterial-based therapeutic strategies for malignant tumors.
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