In the silent battle within, light becomes a precise weapon against disease.
Imagine a treatment that can seek out and destroy cancer cells with the precision of a guided missile, leaving healthy tissue untouched. Or a therapy that can eliminate antibiotic-resistant bacteria by simply shining a light on them. This isn't science fiction—it's the rapidly advancing field of photosensitisation.
At its core, photosensitisation is a process where certain chemicals, called photosensitisers, become activated by light energy and initiate powerful biochemical reactions 2 . While this might sound like an obscure laboratory concept, versions of this process are actually found throughout nature.
The flowering plant Sanguinaria canadensis, or bloodroot, exudes a milk containing sanguinarine, a photosensitiser that coats herbivorous insects and causes photodamage in daylight—a natural pesticide 2 . Similarly, the parasitic fungus Hypocrella bambusae uses condensed aromatic pigments called hypocrellins to break down plant cell walls 2 .
Today, researchers are leveraging this ancient natural principle to develop revolutionary medical treatments that could change how we combat diseases from cancer to antibiotic-resistant infections.
The magic of photosensitisation lies in the unique behavior of certain molecules when they absorb light. These photosensitisers possess resonating structures, often with tricyclic configurations and aromatic rings, that allow them to absorb specific wavelengths of light, typically in the ultraviolet or visible spectrum 7 .
The process follows these key steps:
In this energized triplet state, the photosensitiser can undergo two types of reactions with oxygen:
The singlet oxygen generated in Type II reactions is particularly destructive to cells—it's estimated that each molecule of phototoxin can produce 10³-10ⵠmolecules of singlet oxygen before being degraded 7 . This reactive oxygen species then attacks lipids in cell membranes, proteins, and nucleic acids, triggering rapid cell death 2 .
| Reaction Type | Mechanism | Primary Output | Clinical Applications |
|---|---|---|---|
| Type I | Electron transfer producing radical ions | Superoxide anion, hydroxyl radical | Works better in low-oxygen environments |
| Type II | Energy transfer to molecular oxygen | Singlet oxygen | Most common approach in photodynamic therapy |
| Photothermal | Non-radiative energy release | Heat | Tissue ablation, soldering |
The medical applications of photosensitisation primarily fall into two categories: destroying unwanted cells (like tumors or microbes) and targeted molecular manipulation.
Photodynamic therapy represents one of the most successful clinical applications of photosensitisation. PDT uses photosensitising drugs that tend to accumulate more in cancer cells than healthy ones 2 . When light of the appropriate wavelength is applied to the tumor area, it activates these drugs, generating singlet oxygen that selectively destroys the malignant cells 2 .
With the growing crisis of antibiotic resistance, PACT has emerged as a promising alternative. Demonstrated as early as 1900 by Raab, who reported inactivation of paramecia using acridine and eosin 2 , this approach is now being refined to combat drug-resistant bacteria. The beauty of PACT is that microbes are unlikely to develop resistance to this oxidative attack 2 .
Hematoporphyrin derivatives faced challenges with impurities, poor photoproperties, and skin photosensitivity 2 .
HistoricalSynthetic candidates based on phthalocyanines, phenothiaziniums, and cyanine dyes with improved properties 2 .
CurrentGenetically encoded photosensitisers that can be targeted to specific cells or cellular compartments 3 .
FutureWhile traditional photodynamic therapy has shown remarkable success, it faces significant limitations: the need for external light sources that cannot penetrate deep into tissues, and the requirement for high-intensity light that can cause thermal damage. These challenges have particularly hampered treatment of deep-seated or large tumors.
The research team created what they termed a "self-driven metronomic photodynamic system" (Sd-PDT) through these key steps:
Neutral red photosensitiser molecules chemically grafted onto the PLL surface 5 .
The resulting construct—dubbed PB@MCs—contained approximately 1×10³ bacterial cells and 0.028 μg of photosensitiser per microcapsule 5 .
The PB@MCs demonstrated remarkable capabilities:
A single injection of PB@MCs successfully eliminated large tumors (>300 mm³) in mouse melanoma and rabbit hepatocarcinoma models 5 .
| Component | Function | Significance |
|---|---|---|
| Vibrio harveyi BB170 | Bioluminescent bacteria | Internal light source without external energy |
| Alginate hydrogel | Encapsulation matrix | Biocompatible, allows nutrient exchange |
| Poly-L-lysine coating | Surface modification | Prevents bacterial escape |
| Neutral red | Photosensitiser | Generates reactive oxygen species |
The field of photosensitisation research relies on specialized tools and reagents. Here are some key components driving innovation:
| Reagent Category | Examples | Research Applications |
|---|---|---|
| Chemical Photosensitisers | Hematoporphyrin derivatives, Phthalocyanines, Phenothiaziniums (Methylene Blue) | Photodynamic therapy, antimicrobial applications 2 |
| Genetically Encoded Photosensitisers (GEPS) | miniSOG, SOPP, KillerRed, LOV-based proteins | Targeted cell ablation, protein inactivation, studying ROS signaling 3 9 |
| Bioluminescent Systems | Vibrio harveyi, Aliivibrio fischeri | Internal light sources for deep-tissue therapy 5 |
| Encapsulation Matrices | Alginate hydrogels, Poly-L-lysine coatings | Cell encapsulation, controlled release systems 5 |
| Detection Reagents | Singlet oxygen sensor greens, ROS indicators | Quantifying reactive oxygen species production 9 |
The implications of photosensitisation research extend far beyond current medical applications. Scientists are exploring how these principles might revolutionize multiple fields:
Combining PDT with immunotherapy to engage the patient's immune system against cancer 3 .
Using genetically encoded photosensitisers that can be targeted to specific cellular compartments or cell types 9 .
Applying photosensitisation principles to develop next-generation solar cells, mimicking natural photosynthesis 8 .
As research continues, we're witnessing the emergence of what might become a fourth pillar of cancer treatment alongside surgery, chemotherapy, and radiation. The unique ability of photosensitisation to selectively target diseased tissue while sparing healthy cells represents a fundamental shift in our therapeutic approach.
The journey from observing how certain plants use sunlight as a defensive weapon to programming bacteria to become microscopic light factories inside our bodies demonstrates the remarkable potential of harnessing natural phenomena for medical advancement. As we continue to decode the molecular secrets of photosensitisation, we move closer to a future where light becomes one of medicine's most precise and powerful tools.