Nanomedicine Applications in Cancer Immunotherapy

Nanomedicine is transforming cancer immunotherapy by enabling precise delivery of immunomodulatory agents, enhancing tumour immunogenicity and overcoming immune-suppressive barriers. Engineered nanoparticles can co-deliver antigens, adjuvants and checkpoint inhibitors to lymphoid tissues or the tumour microenvironment, provoking robust cytotoxic T-cell responses. By integrating modalities such as photodynamic or photothermal therapy, starvation therapy and sonodynamic activation, nanocarriers elicit immunogenic cell death and locally release immune agonists with spatiotemporal control, minimising off-target toxicity. Advanced designs exploit stimuli-responsive linkers or enzyme-activated prodrugs to ensure that immunostimulatory activity is confined to malignant sites. This convergence of materials science and immunology holds promise for augmenting the efficacy of checkpoint blockade, reducing metastasis and establishing durable antitumour memory.

Research from Nature Portfolio

Recent studies have exploited deep-tissue stimuli to regulate immune activation with high precision. One approach employs a polymeric pro-nanoagonist activated by second near-infrared (NIR-II) light. Upon NIR-II irradiation, localized photothermal heating cleaves a thermo-responsive linker, releasing a caged immune agonist in solid tumours and inducing immunogenic cell death. This spatiotemporal control augments cytotoxic T lymphocyte infiltration and inhibits distant metastases. In a complementary strategy, semiconducting polymer nano-PROTACs combine light-triggered phototherapy with proteolysis targeting of immunosuppressive enzymes. Near-infrared photoirradiation induces tumour cell death and concurrently activates a PROTAC moiety that degrades key metabolic checkpoints, reshaping the tumour microenvironment to favour effector T-cell function. More recently, sonodynamic immunotherapy formulations have been developed in which semiconducting polymer nanoparticles generate singlet oxygen under ultrasound while cleaving ¹O₂-labile linkers to release immunomodulators specifically at the tumour site. This precision sono-immunotherapy debulks tumours, reprograms the microenvironment and prevents relapse, with reduced systemic immune-related adverse events.

Nanomedicine Applications in Cancer Immunotherapy publication trend

The graph below shows the total number of articles in nanomedicine applications in cancer immunotherapy across all publications each year (not limited to Nature Index journals).

Technical terms

Nanomedicine: Use of nanoscale materials for diagnosis, delivery and modulation of biological functions in medicine.

Photodynamic therapy (PDT): Treatment using light-activated photosensitisers to generate reactive oxygen species and induce cell death.

Immunogenic cell death (ICD): Form of cell death that triggers an adaptive immune response by releasing danger signals and tumour antigens.

Checkpoint inhibition: Therapeutic blockade of immune-inhibitory receptors (e.g. PD-1, CTLA-4) to restore T-cell activity against tumours.

Proteolysis targeting chimera (PROTAC): Bifunctional molecule that induces selective degradation of target proteins via the ubiquitin–proteasome pathway.

Near-infrared II (NIR-II): Light in the 1,000–1,700 nm range, offering deep tissue penetration with minimal phototoxicity.

Sonodynamic therapy: Use of ultrasound-activated agents to produce cytotoxic reactive oxygen species within tissues.

References

1. Activatable polymer nanoagonist for second near-infrared photothermal immunotherapy of cancer. Nature Communications (2021).
2. Semiconducting polymer nano-PROTACs for activatable photo-immunometabolic cancer therapy. Nature Communications (2021).
3. Precision cancer sono-immunotherapy using deep-tissue activatable semiconducting polymer immunomodulatory nanoparticles. Nature Communications (2022).
4. A tumor microenvironment responsive biodegradable CaCO3/MnO2- based nanoplatform for the enhanced photodynamic therapy and improved PD-L1 immunotherapy. Theranostics (2019).
5. Janus Nanobullets Combine Photodynamic Therapy and Magnetic Hyperthermia to Potentiate Synergetic Anti‐Metastatic Immunotherapy. Advanced Science (2019).