**3. Mechanism of photodynamic effect**

treatment of different human diseases by means of small particles, known as nanoparticles

The nanoparticles are known by their large surface area, high reactivity, high solubility, reduced side effects and low toxicity [7-9]. The main nanoparticles applied in nanomedicine are: polymeric nanoparticles, liposomes and lipid nanoparticles, micelles, microcapsules, magnetic particles, and carbon nanoparticles (fullerenes, carbon nanotubes, carbon nanofibers,

Photodynamic therapy (PDT) as a part of photochemotherapy, is a concerted method where, in addition to light and an administered drug, oxygen is required. PDT represents a concerted action of light, with a sensitizers and an oxygen active specie (singlet oxygen) which prefer‐ entially actions on tumor cells and not on healthy cells. The administered drug is generally a substance which can efficiently photosensitize the formation of singlet oxygen (or other reactive species derived from oxygen), and such species react with different biological targets, and cause cellular damage and finally, the cellular death. Activation of the photosensitizers by light is an essential condition for a successful PDT. Doses of light energy applied in PDT

Under such circumstances, this chapter offers the most up–to–date coverage of photodynamic therapy including information on how nanosensitizers, have evolved within the field of cancer therapy and more recently for drugs controlled release in this field, by using personal data

Photodynamic therapy is dating from ancient time, the Indian civilizations reported from the

Niels Fiensen used UV light to treat small pox, pustular infections eruptions, cutaneous tuberculosis, and for its results he obtained the Nobel Prize in Medicine in 1903. Similar results obtained Niels Raab in 1905, by using eosin as sensitizer and combining his results with Jesionek and J.Prime results for skin tumors and epilepsy generated by light induced dermatitis [17]. Meyer-Betz was the only experimentalist who tested this method on himself, by injecting haematoporphyrin, reporting the observed effects: oedema, erythema and light sensitivity [18]. Later, Campbell and Hill studied the PDT effects on microcirculation, reporting the

Lipson in 1966 went on to treat a patient with a large cancer of the breast following an injection of a derivative of haematoporphyrin (HpD). The modern era of photodynamic therapy was established by Dr. T.J.Dougherty, at the Division of Radiation Biology at Roswell Park Memorial Institute, Buffalo, USA, who reported that a systematically injected porphyrin on activation with red light caused complete eradication of transplanted

first time the combined action of psoralens with sunlight to treat vitiligo [14].

, though doses may vary from 25 to 500 W/cm2

depending

with sizes of 2-100 nm.

254 Advances in Bioengineering

etc) and the nanoassemblies [10-12].

are commonly within 60-200 J/cm2

correlated with literature reports.

thrombosis and vascular shutdown [19].

experimental tumors [20].

**2. Short history**

on indications, tissues and light sources [13].

The photodynamic effect mainly results from energy and/or electron transfer of the lowest excited triplet state T1 of the photosensitizer to an organic substrate or molecular oxygen. In the photodynamic therapy occur three types of mechanisms:

**• type I mechanism** – *electron transfer (eT)* where the photosensitizer excited state generates a radical species, for example by electron transfer from (or to) a substrate, or by hydrogen atom abstraction from a substrate. The radical species then reacts with ground state oxygen so that the overall reaction is a photochemically initiated autoxidation:

$$Sens \xrightarrow{h\nu} Sens^\*$$

$$Sens^\* + A \xrightarrow{\circ\tau} Sens^{\bullet\bullet} + A^{-\bullet}$$

$$Sens^\* + AH\_2 \xrightarrow{H \text{ atom transfer}} SensH^\bullet + AH^\bullet$$

$$AH^\bullet + \ ^3O\_2 \longrightarrow AH-OO^\bullet \longrightarrow products$$

(Sens = sensitizer; A = biomolecule; 3 O2 = triplet excited state of oxygen)

**Sheme 1.** The type I mechanism of PDT

**• In type II mechanism** - *energy transfer (ET)* an energy transfer occurs from the excited photosensitizer to molecular oxygen, to give the sensitizer in its ground state and singlet oxygen. In this mechanism electronic excitation energy is transferred from the excited triplet T1 of the sensitizer (generated by intersystem crossing isc from the ecited singlet S1) to triplet molecular oxygen, to give the sensitizer in its ground state S0 and singlet oxygen 1 O2.

**Sheme 2.** The type II mechanism of PDT

Major biological targets are membranes that undergo rupture and the cells are destroyed through the membranes around the mitochondria and the lysosomes. These organelles induce subsequent cellular destruction by necrosis or apoptosis [21-24].

Except these two types of mechanisms, there is another one: **type III mechanism**, which take place when the oxygen is absent in the system.

**Sheme 3.** The type III mechanism of PDT (a)AH = porphyrin; B = quinone (b)Don = donor (cysteine); A = porphyrin; Acc = acceptor (methyl viologen)
