Nitric Oxide-Based Nanomedicine for Cancer Therapy

Nitric oxide-based nanomedicine exploits the unique biological activities of nitric oxide (NO) to enhance anticancer efficacy through precise delivery and controlled release within the tumour microenvironment. NO, a small gaseous messenger, regulates vascular tone, immune function and cell death pathways. In cancer therapy, exogenous NO can normalise aberrant tumour vasculature, increase tumour perfusion and promote immunogenic cell death, while at higher concentrations it directly induces apoptosis or pyroptosis. However, the high reactivity and short half-life of NO pose significant delivery challenges. Nanotechnology addresses these issues by incorporating NO donors into stimuli-responsive platforms—such as light-activated chromophores, thermosensitive polymers or ultrasound-responsive particles—to achieve spatiotemporal control over release. Furthermore, nanoparticle carriers can be engineered for active tumour targeting via surface ligands, passive accumulation through the enhanced permeability and retention effect, and combination therapies that synergise NO with photothermal, photodynamic, chemotherapeutic or immunotherapeutic modalities. Such multifunctional nanoassemblies not only amplify anticancer potency but also mitigate systemic toxicity, offering a versatile toolkit for precision oncology and immunomodulation.

Research from Nature Portfolio

Innovative chemotactic nanomotors have been developed to navigate the glioblastoma microenvironment by harnessing overexpressed reactive oxygen species and inducible nitric oxide synthase as chemoattractants. These self-propelled nanosystems are surface-functionalised with a blood-brain-barrier targeting peptide and loaded with a mitochondrial-directed anti-tumour agent. On reaching the tumour, autonomous NO release synergises with mitochondrial disruption to trigger immunogenic cell death, promote dendritic cell maturation and facilitate cytotoxic T-cell infiltration, culminating in durable immune memory that suppresses tumour recurrence. In parallel, a thermosensitive hydrogel has been engineered from biocompatible polymers to co-deliver an NO donor and immune-checkpoint-blocking antibody. Upon injection, the matrix forms an in situ depot that responds to the acidic tumour milieu, steadily releasing both agents to remodel local and draining-lymph-node immune networks, thereby enhancing both local tumour control and distant abscopal effects.

Nitric Oxide-Based Nanomedicine for Cancer Therapy publication trend

The graph below shows the total number of articles in nitric oxide-based nanomedicine for cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Nitric oxide donor: A chemical precursor that releases NO under defined stimuli.

Photothermal therapy (PTT): A treatment modality that uses near-infrared light to convert photon energy into heat for tumour ablation.

Chemotaxis: Directed movement of nanocarriers in response to chemical gradients.

Thermosensitive hydrogel: A polymer network that undergoes sol–gel transition at physiological temperatures to form a drug-releasing depot.

Enhanced permeability and retention (EPR) effect: Passive accumulation of nanoparticles in tumour tissue due to leaky vasculature and impaired lymphatic drainage.

Pyroptosis: A form of programmed cell death characterised by inflammatory cytokine release and membrane pore formation.

References

1. A nitric-oxide driven chemotactic nanomotor for enhanced immunotherapy of glioblastoma. Nature Communications (2023).
2. Thermosensitive hydrogel releasing nitric oxide donor and anti-CTLA-4 micelles for anti-tumor immunotherapy. Nature Communications (2022).
3. Emerging nitric oxide gas‐assisted cancer photothermal treatment. Exploration (2024).
4. Record‐High Ultrasound‐Sensitive NO Nanogenerators for Cascade Tumor Pyroptosis and Immunotherapy. Advanced Science (2023).