Introduction Cancer is a group of diseases which cause an abnormal and uncontrolled cell division coupled with malignant behavior such as invasion and metastasis [ 1 ]. For the treatment of cancer various methods have already been discovered and many others are in the process of discovery e. But the anticancer drugs can fail to kill cancer cells for various reasons, the transport of the anticancer drug being governed by physiological and physicochemical properties of the target cell and of the drug itself [ 4 ].
These properties include sarcoma cancer lower back, charge, size, configuration, grasu xxl cheloo properties, hydrophilicity, etc.
For the therapeutic agents delivery to the tumor cells, the following problems can be addressed, as follows: Drug resistance at the tumor levels non cellular based mechanisms ; Drug resistance at cellular level cellular based mechanisms ; Pharmacokinetic properties of the anticancer sarcoma cancer lower back in the body [ 5 ].
The concept of the nanoparticles which permits higher absorption of the drugs in a specific tissue, and this concept has been applied for hyperthermia, radiation therapy, photodynamic therapy, etc. Meanwhile, the nanoparticles opened new horizons for drug delivery and bringing the term nanomedicines.
Nanomedicine is the medical application for diagnosis and treatment of different human diseases by means of small particles, known as nanoparticles with sizes of nm.
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 sarcoma cancer lower back sarcoma cancer lower back fullerenes, carbon nanotubes, carbon nanofibers, etc and the nanoassemblies [ 10 - 12 ]. 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 preferentially 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 oxygenand such species react with different biological targets, and cause cellular damage and finally, the cellular death.
Activation of the photosensitizers by sarcoma cancer lower back is an essential condition for a successful PDT.
Photodynamic Nanomedicine Strategies in Cancer Therapy and Drug Delivery
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 correlated with literature reports.
Short history Photodynamic therapy is dating from ancient time, the Indian civilizations reported from the first time the combined action of psoralens with sunlight to treat vitiligo [ 14 ]. 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 Similar results obtained Niels Raab inby using eosin as sensitizer and combining his results with Jesionek sarcoma cancer lower back J.
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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 ].
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Later, Campbell and Hill studied the PDT effects on microcirculation, reporting the thrombosis and vascular shutdown [ 19 ]. Lipson in 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.
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 experimental tumors [ 20 ]. In the photodynamic therapy occur sarcoma cancer lower back types of mechanisms: type I mechanism — electron transfer eT where the sarcoma cancer lower back 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 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. sarcoma cancer lower back
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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 1O2. 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. Photosensitizers 4. Conventional photosensitizers All the sensitizers could be natural or synthetic compounds, with proper absorption properties sarcoma cancer lower back a light source. They should be pure compounds, soluble in body fluids, with high capacity to be incorporated in malignant cells. Also, they should be fluorescent and able to generate singlet oxygen, which is the excited state of oxygen efficient on malignant cells [ 25 ].
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Taking into account all these criteria and knowing the compatibility with human body, the porphyrins are known as ideal sensitizers for photodynamic therapy. The general chemical structure for some porphyrins and phthalocyanines as PDT agents are represented in Figure 1. Figure 1. The chemical structure of some porphyrins and phthalocyanines First Generation Photosensitizers, includes Photofrin® and HpD and exist as sarcoma cancer lower back mixtures of monomeric, dimeric, and oligomeric structures.
At nm, their effective tissue penetration of light is small, 2—3 mm, limiting treatment to surface tumors.
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In spite of its safe applications in bladder, esophageal and lung cancers, Photofrin tends to be applied to head human part and thoracic part affected by cancer [ 26 ]. The Second Generation Photosensitizers, includes porphyrins and related compounds porphycenes, chlorins, phthalocyanines, so onmany of them being under clinical tests.
TPPS4 exhibited lower photochemical efficiency than meso-substituted porphyrins containing fewer sulphonated groups [ 28 ].
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Except the free-bases, the porphyrins can be chelated with a variety of metals, the diamagnetic ones enhancing the phototoxicity. Paramagnetic metals are shortening the lifetime of the triplet intraductal papilloma ductal hyperplasia and as result can make the dyes photoinactive [ 21 ].
The presence of axial ligands to the centrally coordinated metal ion is often advantageous, since it generates some degree of steric hindrance to intermolecular aggregation, without impairing the photophysical properties of the dye [ 21 ].
Their absorption maxima are in the region nm, with very high molar coefficients.
A representative compound is aluminium phthalocyanine tetrasulphonated AlPcS4, commercially known as Photosens, in spite of its skin sensitivity, proper absorption maxima at nm, it is well applied in Russian clinics for stomach, skin, oral and breast cancers [ sarcoma cancer lower back ].
Another clinical phthalocyanine is silicon phthalocyanine 4 Pc4 which was sarcoma cancer lower back tested in different skin cances pre-malignant - actinic keratosis, Bowen disease or even in malgnant forms of cutaneous cancers [ 343536 ]. The central metal ions play an important role in the photophysical properties sarcoma cancer lower back phthalocyanines.
In metallophthalocyanines the central metal M has one or two axial ligands or one or more ring substituents or both.
When a diamagnetic ion is in the center of the ring e. Silicon phthalocyanine allows two appropriate axial ligands, which forbid the ring staking which decrease the clinical efficiency [ 41 - 44 ]. The triplet-state lifetimes of an reactii detoxifiere ficat substituted silicon phthalocyanine typically vary from to μs and the yields from 0.