Photodynamic Therapy and Targeted Drug Delivery Systems

Photodynamic therapy (PDT) harnesses light-activated photosensitisers to produce reactive oxygen species, notably singlet oxygen, within diseased tissues, enabling selective cytotoxicity with minimal systemic toxicity. By integrating targeted drug delivery systems—including nanocarriers, prodrugs and caged compounds—PDT efficacy and specificity have been markedly enhanced. Modern approaches employ multifunctional nanoplatforms that co-encapsulate photosensitisers and chemotherapeutics within stimuli-responsive architectures, allowing spatiotemporally controlled release under external triggers such as visible or near-infrared light, X-rays or ionising radiation. Recent advances emphasise deep-tissue activation strategies via radioswitches and radiotherapy-induced bond cleavage, overcoming the penetration limits of conventional light sources. Concurrently, prodrug designs incorporating radiation- or singlet-oxygen-sensitive linkers enable on-demand conversion to active drugs at the tumour site, minimising off-target effects. Active targeting via ligands and antibodies further refines biodistribution, while stimuli-responsive materials enable hierarchical release profiles. Combined photochemical–immunological protocols have exhibited durable systemic immunity and abscopal effects, underscoring the global clinical potential of integrated photodynamic and targeted drug delivery strategies.

Research from Nature Portfolio

Recent studies have introduced a radioswitch concept whereby high-energy ionising radiation triggers local energy conversion to activate photosensitive azobenzene derivatives at arbitrary depths. This approach, compatible with gamma-ray dosages used in radiotherapy, induces cytotoxic effects selectively in irradiated cancer cells, surmounting the millimetre-scale penetration limit of traditional PDT and opening avenues for deep-tissue photoactivated treatments.

Photodynamic Therapy and Targeted Drug Delivery Systems publication trend

The graph below shows the total number of articles in photodynamic therapy and targeted drug delivery systems across all publications each year (not limited to Nature Index journals).

Technical terms

Photodynamic therapy: A treatment modality using light-activated photosensitising agents that generate cytotoxic reactive oxygen species to destroy target cells.

Photosensitiser: A molecule that, upon light absorption, transfers energy to molecular oxygen to produce reactive oxygen species.

Prodrug: An inactive precursor of a therapeutic agent that is converted into its active form in response to specific stimuli.

Radioswitch: A photosensitive compound engineered to undergo bond cleavage or structural change upon exposure to ionising radiation.

Nanocarrier: A nanoscale vehicle designed to deliver therapeutic agents selectively to biological targets and control release kinetics.

Caged compound: A molecule whose bioactive moiety is temporarily inactivated by a photolabile protecting group until triggered by radiation or light.

Immunogenic cell death: A form of cell death that stimulates an adaptive immune response against tumour antigens.

References

1. Visible light-induced singlet oxygen-mediated intracellular disassembly of polymeric micelles co-loaded with a photosensitizer and an anticancer drug for enhanced photodynamic therapy. Chemical Communications (2015).
2. Development of Prodrugs for PDT-Based Combination Therapy Using a Singlet-Oxygen-Sensitive Linker and Quantitative Systems Pharmacology. Journal of Clinical Medicine (2019).
3. Breaking photoswitch activation depth limit using ionising radiation stimuli adapted to clinical application. Nature Communications (2022).
4. Theoretical Design and Synthesis of Caged Compounds Using X‐Ray‐Triggered Azo Bond Cleavage. Advanced Science (2024).
5. Targeted Radionuclide Therapy Activates Prodrugs for Treating Metastasis. ACS Central Science (2024).
6. Self-polymerized platinum (II)-Polydopamine nanomedicines for photo-chemotherapy of bladder Cancer favoring antitumor immune responses. Journal of Nanobiotechnology (2023).