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Photodynamic Therapy (PDT) — Advances 2024–2025 ​

Note: This page is educational and reflects the state of the literature in 2025. It does not replace medical advice.

TL;DR ​

Photodynamic Therapy (PDT) uses three components — a photosensitizer (PS) drug, light of a specific wavelength, and molecular oxygen — to produce reactive oxygen species (ROS) that selectively kill tumor cells. PDT is approved for several skin, head & neck, esophageal, lung, bladder, and biliary indications. The 2024–2025 advances are concentrated in third-generation photosensitizers, nanoparticle delivery, near-infrared (NIR) activation for deeper tissue, and PDT + photothermal (PTT) and immunotherapy combinations. Sources: [1], [2]

1. The three-component mechanism ​

The classic PDT photoreaction:

  1. Photosensitizer is administered (systemic or topical) and accumulates in tumor tissue.
  2. Light at the PS-absorbing wavelength reaches the tumor (usually via laser through fiber optics or LED for skin).
  3. The excited PS transfers energy to molecular O₂, generating singlet oxygen (¹O₂) and other ROS.
  4. ROS damage cellular components — membranes, mitochondria, lysosomes, DNA — triggering apoptosis, necrosis, autophagy.
  5. Vascular shutdown and immune activation contribute to durable tumor control. Sources: [1], [2]

PDT is fundamentally local — the drug is inert without light, so toxicity is confined to illuminated areas.

2. The classical photosensitizers ​

GenerationExamplesNotes
1stHematoporphyrin derivatives (HpD, Photofrin / porfimer sodium)Approved 1990s; long skin photosensitivity (~6 weeks)
2nd5-ALA / methyl-ALA, m-THPC (Foscan / temoporfin), verteporfin (Visudyne), talaporfinBetter targeting, shorter photosensitivity windows
3rdTargeted conjugates, nanocarrier-encapsulated, antibody- and aptamer-targeted PSTumor-specific accumulation, improved pharmacology[2]

5-ALA-based PDT is widely used in dermatology (actinic keratosis, basal cell carcinoma) and as a fluorescence guide in glioblastoma surgery (5-ALA fluorescence, not strictly PDT but related).

3. Where PDT is used clinically ​

  • Dermatology — actinic keratosis, basal cell carcinoma (superficial), Bowen's disease, photodynamic acne therapy.
  • Head and neck — early oral cavity and oropharyngeal cancers.
  • Esophagus — Barrett's high-grade dysplasia, palliation of obstructing esophageal cancer.
  • Lung — endobronchial obstructing tumors (palliation), early central lung cancers.
  • Bladder — selected non-muscle-invasive cases.
  • Biliary tree — cholangiocarcinoma palliation.
  • Brain (research) — 5-ALA in glioma surgery for fluorescence-guided resection.
  • Ophthalmology — verteporfin for choroidal neovascularization (not strictly cancer).

4. The 2024–2025 advances ​

Third-generation and targeted photosensitizers ​

Nanoparticle delivery, antibody conjugates, peptide and aptamer targeting all aim to improve tumor-to-normal selectivity beyond passive accumulation. Nanocarrier strategies include lipid nanoparticles, polymeric micelles, MOFs, and silica-based platforms. Sources: [2]

NIR activation for deeper tissue ​

Visible light penetrates only a few millimeters into tissue. Newer photosensitizers absorbing in the near-infrared "tissue window" (~700–900 nm) allow treatment of deeper lesions. Two-photon excitation is also under investigation.

Light delivery hardware ​

  • Implantable micro-LED light sources for sustained intratumoral illumination.
  • Endoscopic and intraluminal fiber delivery for deep-organ targets.
  • Image-guided fiber placement under MRI/CT/US guidance.
  • Daylight PDT for actinic keratosis (uses ambient light instead of clinic lamp — patient-friendly).

Combination therapies ​

  • PDT + photothermal therapy (PTT) — multimodal nanoparticles deliver both ROS and heat, exploiting non-overlapping toxicities for synergy. Sources: [1]
  • PDT + immunotherapy — PDT-induced immunogenic cell death pairs naturally with checkpoint inhibitors and other IO; multiple combination trials in melanoma and head & neck.
  • PDT + chemotherapy — selective sensitization.
  • PDT + radiation — hypoxic-modifier strategies (PDT consumes O₂, paradoxically of interest in fractionated combinations).

Fluorescence-guided resection (FGR) ​

Increasingly common in glioma (5-ALA), bladder (HAL/HAL hexvix), and gastrointestinal surgery. Same chemistry as PDT, used diagnostically.

5. Limitations to be honest about ​

  • Depth limitation — light penetration limits PDT to superficial or accessible deep targets (with fiber).
  • Oxygen dependence — hypoxic tumors respond worse.
  • PS solubility and pharmacokinetics — many PSs are poorly soluble or aggregate; nanoformulations help.
  • Skin photosensitivity — patients must avoid sunlight after some PSs (less of an issue for newer agents).
  • Heterogeneous PS uptake — tumor coverage may be incomplete.
  • Lack of large randomized trials vs. standard care for many indications — most evidence is single-arm or small comparative.

6. What technologists can build ​

  • Light-dose planning — Monte Carlo simulation of light propagation in tissue, integrated with imaging.
  • Real-time dosimetry — fluorescence sensors, oxygen probes, ROS sensors in the treatment field.
  • Image-guided fiber placement — robotic and software guidance for implantable light delivery.
  • Treatment-response prediction — ML on PS uptake imaging + tumor characteristics.
  • Combination optimization — predict best PDT + IO/PTT/chemo schedules.

7. Brazilian context ​

  • USP São Carlos (Instituto de Física, Centro de Pesquisa em Óptica e Fotônica — CEPOF) is internationally recognized for clinical and translational PDT research, particularly in skin and oral cancer in low-resource settings.
  • Domestic photosensitizers and LED light-source projects have driven down cost for primary-care use of PDT in dermatology in some regions of Brazil.
  • ANVISA-registered PDT systems and PSs are limited; academic-clinical programs anchor much of the local activity.
  • The CEPOF/USP São Carlos mobile units delivering PDT to municipalities is one of the most cited social-impact PDT programs globally.

See also ​

References ​

  1. Overchuk M, Weersink RA, Wilson BC, Zheng G. Photodynamic and Photothermal Therapies: Synergy Opportunities for Nanomedicine. ACS Nano 2023;17:7979-8003. PMID 37129253. https://doi.org/10.1021/acsnano.3c00891
  2. Kwiatkowski S, Knap B, Przystupski D, et al. Photodynamic therapy — mechanisms, photosensitizers and combinations. Biomed Pharmacother 2018;106:1098-1107. PMID 30119176. https://doi.org/10.1016/j.biopha.2018.07.049
  3. U.S. National Cancer Institute. Photodynamic therapy. https://www.cancer.gov/about-cancer/treatment/types/photodynamic-therapy
  4. American Cancer Society. https://www.cancer.org/cancer.html
  5. Cleveland Clinic. Cancer (overview). https://my.clevelandclinic.org/health/diseases/12194-cancer
  6. A.C. Camargo Cancer Center. https://accamargo.org.br
  7. Fundação do Câncer (Brasil). https://www.cancer.org.br/
  8. Ministério da Saúde / BVS. ABC do câncer. https://bvsms.saude.gov.br/bvs/publicacoes/abc_do_cancer.pdf
  9. ANVISA — Agência Nacional de Vigilância Sanitária. https://www.gov.br/anvisa/pt-br
  10. CEPOF / IFSC-USP São Carlos. https://www.ifsc.usp.br/

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