Understanding Photodynamic Therapy: Principles & Mechanisms of Light-Activated Cancer Trea, Slides of Medicine

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Presented By:

Rashid Mahmood

Chapter# 12 LIGHT-ACTIVATED

THERAPY: PHOTODYNAMIC THERAPY

Objective

Introduction to PDT

Photsensitizer

Mechanism of cell Death

Light Irradation for PDT

Two Photons PDT

Current Research & Future

Directions

Light_Activated Therapy: Photodynamic

Therapy (PDT)

The therapeutic properties of light have been known for thousands of years, but it was only in the last century that photodynamic therapy (PDT) was developed.

Photodynamic therapy or PDT is a treatment that uses special drugs, called photosensitizing agents, along with light to kill cancer cells.The drugs only work after they have been activated or "turned on" by certain kinds of light.

PDT is also called photoradiation therapy, phototherapy.

Three Components are required for PDT

simultaneously:

 Photosensitizer

 Cellular Oxygen

 Light of suitable wavelength

Continued:

Photons

Triplet Drug Oxygen

PDT

Photosensitiser (PS) is administered,

usually by injection or a cream placed on the

skin. After some accumulation time ( in vivo)

light is directed onto the tissue containing

the drug, the drug becomes activated and

destroys the tissue.

How does PDT work?

Photosensitizer (PS) is injected into the body

The tumor is selectively destroyed

The PS concentrates at the tumor sites.

The chemical is activated by the light docsity.com

Contd……….

Type II Reaction:

The photosensitizer in the target tissue is

excited as before to its lowest energy triplet state

and then transfers its excess energy to molecular

oxygen present in the tissue to form a particularly

reactive species called 'singlet oxygen’( amount of

energy, 22 kcal/mol, is required).This excited

oxygen oxidizes and destroys target tissue.

After the transfer of energy, the photosensitizer

returns to its starting point, where it is available

to begin the whole process again.

PHOTOSENSITIZERS (PS)

The compounds having stable electronic configuration and whose ground state is in a singlet state but upon exposure to light , the absorbed photon convert the compound into higher energy state are called photosensitizers.

Photosensitiser is administered, usually by injection or a cream placed on the skin. After some accumulation time light is directed onto the tissue containing the drug, the drug becomes activated and destroys the tissue

PROPERTIES OF AN IDEAL PS

Chemical purity, homogeneity and good stability

High quantum yield of 1 O 2 & other reactive oxygen

species.

High triplet-state yields and long triplet-state lifetime.

Selective accumulation in cancer tissue.

No toxicity in the absence of light and be cytotoxic

only upon photo activation.

Have high molar extinction coefficient ( or molar

absorption coefficient) and high absorbance.

FDA Approved Photosensitisers

Several photosensitizers are commercially available for

clinical use, such as

• Porphyrin Derivatives:

The first group of photosensitizers used in clinical PDT were hematoporphyrin derivatives. Photofrin® is a di-acid and is composed of differing fractions of oligomers (85%) ,porphyrin monomers and dimers, which are required for successful therapy [31-32]. Its chemical formula is C68H74N8 O11 ,with molecular weight of 1179. g/mol.

From figure 2 it is clear that absorption peaks lies between 400~650 nm and all the Porphyrines exhibits weak absorption maxima around 630 nm.

Chlorins and Bacteriochlorins

Benzoporphyrins are fused-ring chlorin derivatives produced by cyclo-addition reactions. The mono-acid benzoporphyrin derivative, called veteroporfin (also labeled BPD-MA), absorbs at 690nm. PDT trials of this photosensitizer show rapid tumor accumulation and reduced skin photosensitivity. A benzoporphyrin derivative has been approved for the treatment of age-related macular degeneration (ARMD).

Advantage over Photofrin® is rapid clearance which is more desirable in PDT.

Another interesting photosensitizer is aminolaevulinic acid which itself is not even a photosensitizer but a precursor of the endogeneous synthesis of porphyrins. According to Q.Ping at el naturally occurring amino acid is converted enzymatically to protoporphyrin. The drug is active at 630 nm, which is adequate for the maximal absorption of ALA. ALA is not highly active, therefore relatively high light energy or long treatments are needed.

Aminolevulinic Acid (ALA):

Figure 3 Molecular structure for ALA.