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Photodynamic therapy

Photodynamic therapy is a physics topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Photodynamic therapy rather than just read about it. In short: Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance used in conjunction with molecular oxygen to elicit cell death (phototoxicity). PDT is used in treating acne, wet age-related macular degeneration, psoriasis, and herpes.

Photodynamic therapy — main illustration
Photodynamic therapy — illustration

Key takeaways

  • Photodynamic therapy belongs to physics; place it in that map before memorising details.
  • Learn the definition first, then one example that makes the definition concrete.
  • Connect Photodynamic therapy to a quantity you can measure, compute or draw — that is where exam questions come from.
  • Reproduce the core statement of Photodynamic therapy from memory before moving on to harder problems.

Reference excerpt

Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance used in conjunction with molecular oxygen to elicit cell death (phototoxicity). PDT is used in treating acne, wet age-related macular degeneration, psoriasis, and herpes. It is used to treat malignant cancers, including head and neck, lung, bladder and skin. Advantages lessen the need for delicate surgery and lengthy recuperation and minimal formation of scar tissue and disfigurement. A side effect is the associated photosensitisation of skin tissue.

Basics PDT applications involve three components: a photosensitizer, a light source and tissue oxygen. The wavelength of the light source needs to be appropriate for exciting the photosensitizer to produce radicals and/or reactive oxygen species. These are free radicals (Type I) generated through electron abstraction or transfer from a substrate molecule and highly reactive state of oxygen known as singlet oxygen (Type II). PDT is a multi-stage process. First a photosensitiser, ideally with negligible toxicity other than its phototoxicity, is administered in the absence of light, either systemically or topically. When a sufficient amount of photosensitiser appears in diseased tissue, the photosensitiser is activated by exposure to light for a specified period. The light dose supplies sufficient energy to stimulate the photosensitiser, but not enough to damage neighbouring healthy tissue. The reactive oxygen kills the target cells.

Reactive oxygen species In air and tissue, molecular oxygen (O2) occurs in a triplet state, whereas almost all other molecules are in a singlet state. Reactions between triplet and singlet molecules are forbidden by quantum mechanics, making oxygen relatively non-reactive at physiological conditions. A photosensitizer is a chemical compound that can be promoted to an excited state upon absorption of light and undergo intersystem crossing (ISC) with oxygen to produce singlet oxygen. This species is highly cytotoxic, rapidly attacking any organic compounds it encounters. It is rapidly eliminated from cells, in an average of 3 μs.

Photochemical processes When a photosensitiser is in its excited state (3Psen*) it can interact with molecular triplet oxygen (3O2) and produce radicals and reactive oxygen species (ROS), crucial to the Type II mechanism. These species include singlet oxygen (1O2), hydroxyl radicals (•OH) and superoxide (O2−) ions. They can interact with cellular components including unsaturated lipids, amino acid residues and nucleic acids. If sufficient oxidative damage ensues, this will result in target-cell death (only within the illuminated area).

Photochemical mechanisms When a chromophore molecule, such as a cyclic tetrapyrrolic molecule, absorbs a photon, one of its electrons is promoted into a higher-energy orbital, elevating the chromophore from the ground state (S0) into a short-lived, electronically excited state (Sn) composed of vibrational sub-levels (Sn′). The excited chromophore can lose energy by rapidly decaying through these sub-levels via internal conversion (IC) to populate the first excited singlet state (S1), before quickly relaxing back to the ground state. The decay from the excited singlet state (S1) to the ground state (S0) is via fluorescence (S1 → S0). Singlet state lifetimes of excited fluorophores are very short (τfl. = 10−9–10−6 seconds) since transitions between the same spin states (S → S or T → T) conserve the spin multiplicity of the electron and, according to the Spin Selection Rules, are therefore considered "allowed" transitions. Alternatively, an excited singlet state electron (S1) can undergo spin inversion and populate the lower-energy first excited triplet state (T1) via intersystem crossing (ISC); a spin-forbidden process, since the spin of the electron is no longer conserved. The excited electron can then undergo a second spin-forbidden inversion and depopulate the excited triplet state (T1) by decaying to the ground state (S0) via phosphorescence (T1→ S0). Owing to the spin-forbidden triplet to singlet transition, the lifetime of phosphorescence (τP = 10−3 − 1 second) is considerably longer than that of fluorescence.

Photosensitisers and photochemistry Tetrapyrrolic photosensitisers in the excited singlet state (1Psen*, S>0) are relatively efficient at intersystem crossing and can consequently have a high triplet-state quantum yield. The longer lifetime of this species is sufficient to allow the excited triplet state photosensitiser to interact with surrounding bio-molecules, including cell membrane constituents.

Photochemical reactions Excited triplet-state photosensitisers can react via Type-I and Type-II processes. Type-I processes can involve the excited singlet or triplet photosensitiser (1Psen*, S1; 3Psen*, T1), however due to the short lifetime of the excited singlet state, the photosensitiser can only react if it is intimately associated with a substrate. In both cases the interaction is with readily oxidisable or reducible substrates. Type-II processes involve the direct interaction of the excited triplet photosensitiser (3Psen*, T1) with molecular oxygen (3O2, 3Σg).

Type-I processes Type-I processes can be divided into Type I(i) and Type I(ii). Type I (i) involves the transfer of an electron (oxidation) from a substrate molecule to the excited state photosensitiser (Psen*), generating a photosensitiser radical anion (Psen•−) and a substrate radical cation (Subs•+). The majority of the radicals produced from Type-I(i) reactions react instantaneously with molecular oxygen (O2), generating a mixture of oxygen intermediates. For example, the photosensitiser radical anion can react instantaneously with molecular oxygen (3O2) to generate a superoxide radical anion (O2•−), which can go on to produce the highly reactive hydroxyl radical (OH•), initiating a cascade of cytotoxic free radicals; this process is common in the oxidative damage of fatty acids and other lipids. The Type-I process (ii) involves the transfer of a hydrogen atom (reduction) to the excited state photosensitiser (Psen*). This generates free radicals capable of rapidly reacting with molecular oxygen and creating a complex mixture of reactive oxygen intermediates, including reactive peroxides.

… excerpt ends here. Continue reading the full article.

Illustrations

Photodynamic therapy illustration
Photodynamic therapy: Modified Jablonski diagram showing the mechanism of PDT[5]
Modified Jablonski diagram showing the mechanism of PDT[5]

Worked examples

Example 1 — a first encounter with Photodynamic therapy

Start with the simplest possible case. Write down what Photodynamic therapy claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In physics, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Photodynamic therapy before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Photodynamic therapy ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Photodynamic therapy

In research
Photodynamic therapy appears in physics research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry
Engineering practice reuses Photodynamic therapy in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom
Photodynamic therapy is common in secondary-school and first-year university syllabi. It links to neighbouring topics Cancer treatments, Laser medicine, Light therapy, so understanding it makes those chapters shorter.
In everyday life
Look for Photodynamic therapy outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Photodynamic therapy in 20 minutes

  1. Read the reference excerpt below once, without taking notes.
  2. Close the page and write down what Photodynamic therapy means in your own words.
  3. Compare your version with the excerpt and mark what you missed.
  4. Work through the three examples above with pen and paper.
  5. Explain Photodynamic therapy out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Photodynamic therapy in simple terms?

Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance used in conjunction with molecular oxygen to elicit cell death (phototoxicity). PDT is used in treating acne, wet age-related macular degeneration, psoriasis, and herpes.

Why does Photodynamic therapy matter?

Because it connects several physics ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Photodynamic therapy?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Photodynamic therapy.

Tags

  • Cancer treatments
  • Laser medicine
  • Light therapy
  • Medical physics

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