Mild-Temperature Photothermal Therapy in Cancer Treatment

Mild-temperature photothermal therapy (MTPTT) uses targeted light-activated materials to raise tumour temperatures to around 42–45 °C, enough to damage cancer cells while sparing healthy tissue. By employing near-infrared lasers and nanomaterials such as gold nanoshells, polymeric nanoparticles or biocompatible hydrogels, this approach offers precise heat delivery with minimal side effects. The chief challenge is thermoresistance driven by heat shock proteins (HSPs) and protective stress responses within tumour cells. To overcome this, researchers are developing multifunctional nanoplatforms that combine heat generation with inhibition of HSP activity, gene silencing via DNAzymes or small interfering RNA, induction of inflammatory cell death pathways like pyroptosis, and synergistic therapies including immunotherapy and metabolic starvation. Preclinical studies demonstrate enhanced tumour regression, improved immune infiltration and long-term protection against recurrence. With advances in stimuli-responsive drug release and imaging-guided treatment, MTPTT stands out as a promising, minimally invasive option in the evolving landscape of cancer care.

Research from Nature Portfolio

Recent studies have unveiled an autocatalytic nanomachine designed to sensitise tumours to mild photothermal treatment by combining DNAzyme-mediated gene regulation with photothermal dyes and chemophores. This modular system employs targeting ligands and biomineralised coatings to release deoxyribozymes and calcium ions in acidic tumour environments, selectively silencing heat shock protein mRNA and potentiating infrared-induced hyperthermia at mild temperatures. Another advance harnesses nanoparticle-mediated blockade of the TRPV1 ion channel to disrupt calcium-dependent heat shock factor 1 activation, thereby downregulating HSP70 expression and remodelling the stroma for enhanced infiltration of immune cells and checkpoint inhibitors. These approaches demonstrate how precise dismantling of cellular self-defences can amplify both the thermal and immune components of mild-temperature photothermal therapy.

Mild-Temperature Photothermal Therapy in Cancer Treatment publication trend

The graph below shows the total number of articles in mild-temperature photothermal therapy in cancer treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Photothermal therapy (PTT): A treatment that uses light-absorbing agents to convert electromagnetic energy into heat for targeted destruction of tumour cells.

Mild-temperature photothermal therapy (MTPTT): A variant of PTT operating at moderate hyperthermia (42–45 °C) to minimise damage to healthy tissues and inflammatory responses.

Heat shock proteins (HSPs): Molecular chaperones that are upregulated under stress and confer thermotolerance to cells by preventing protein misfolding.

DNAzyme: A catalytically active DNA molecule engineered to cleave specific RNA sequences, used here to silence heat shock protein mRNA.

Pyroptosis: A form of programmed cell death characterised by inflammatory caspase activation, membrane pore formation and ATP depletion.

Transient receptor potential vanilloid member 1 (TRPV1): A calcium-permeable channel whose blockade can prevent heat-induced activation of stress response pathways.

References

1. An autocatalytic multicomponent DNAzyme nanomachine for tumor-specific photothermal therapy sensitization in pancreatic cancer. Nature Communications (2023).
2. Enhanced mild-temperature photothermal therapy by pyroptosis-boosted ATP deprivation with biodegradable nanoformulation. Journal of Nanobiotechnology (2023).
3. Laser‐Triggered Small Interfering RNA Releasing Gold Nanoshells against Heat Shock Protein for Sensitized Photothermal Therapy. Advanced Science (2016).
4. Nanoparticle-mediated TRPV1 channel blockade amplifies cancer thermo-immunotherapy via heat shock factor 1 modulation. Nature Communications (2023).
5. Enhancing the Efficiency of Mild-Temperature Photothermal Therapy for Cancer Assisting with Various Strategies. Pharmaceutics (2022).