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 sarcoma cancer research uk physiological and physicochemical properties of the target cell and of the drug itself [ 4 ].
These properties include pressure, charge, size, configuration, electrochemical 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 sarcoma cancer research uk the anticancer agent 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 sarcoma cancer research uk diseases by means of small particles, known as nanoparticles with sizes of nm.
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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 research uk nanoparticles 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.
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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 sarcoma cancer research uk targets, and cause cellular damage and finally, the cellular death. Activation of the photosensitizers by light is an essential condition for a successful 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 correlated with literature reports.
Short history Photodynamic therapy is dating from ancient time, the Indian civilizations reported from the first time the sarcoma cancer research uk action of psoralens with sunlight to treat vitiligo [ 14 ]. Niels Fiensen used Sarcoma cancer research uk 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 sarcoma cancer research uk 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 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, Sarcoma cancer research uk, 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 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 type I mechanism of PDT In type II mechanism - energy transfer ET an energy transfer occurs from the sarcoma cancer research uk 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 sarcoma cancer research uk 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 sarcoma cancer research uk 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 from 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 ]. Taking into account all these criteria and knowing the compatibility with human body, the porphyrins are known as sarcoma cancer research uk 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 Sarcoma cancer research uk and exist as complex mixtures of monomeric, dimeric, and oligomeric structures. At nm, their effective tissue penetration of sarcoma cancer research uk is small, 2—3 mm, limiting treatment to surface tumors.
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 ].
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 state 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 sarcoma cancer research uk photophysical properties of the dye [ 21 ].
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Sarcoma cancer research uk 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 [ 33 ].
Another clinical phthalocyanine is silicon phthalocyanine 4 Pc4 which was successful tested in cervical cancer risks 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 of phthalocyanines. In metallophthalocyanines the central metal M has one or two axial sarcoma cancer research uk or one or more ring substituents or both.
When a diamagnetic ion is in the center of the ring e.
Preventing unnecessary cancer treatment - Cancer Research UK
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 axially substituted silicon phthalocyanine typically vary from to μs and the yields from 0.
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Some synthetic silicon phthalocyanine and naphthalocyanine Figure 2 have been used sarcoma cancer research uk some laboratory experuiments on K culture cellk with excellent results [ 4546 ]. Third generation photosensitizers contains available drugs that are modified them with antibody conjugates, biologic conjugates, etc. These terms are still being used although not accepted unanimously and dividing photosensitizing drugs into such generations may be very confusing.
The nanostructures are increasingly being used as carriers for the development of 3rd generation PS, as the most important drug delivery systems used as carriers for PS in the field of anticancer PDT. Figure 2.
Nanoparticles have unusual properties that can improve the drug delivery. Hard nanoparticles Inorganic Nanoparticles is the generic term for several nanoparticles including for example metal oxide- and non-oxide ceramics, metals, gold and magnetic nanoparticles.
Ceramic nanoparticles: Ceramic-based nanoparticles have some advantages over organic carriers: particle size, shape, porosity, and mono-dispersibility. They are water-soluble, extremely stable, and known for their compatibility in biological systems without being subjected to microbial attack.
Photodynamic Nanomedicine Strategies in Cancer Therapy and Drug Delivery
For conventional drug delivery, the carrier vehicle should release the encapsulated drug at the target tissue. Their silica-based nanoparticles diameter ca. The resulting silica- based nanoparticles were monodispersed with uniform particle size. By irradiation with suitable wavelengths: or nm, silica nanoparticles with porphyrin embedded, could be efficiently taken up by tumor cells and lead to cells death.
Silica wart tongue pain SiO2with the following advantages: chemically inert, sarcoma cancer research uk interactions with other molecules in the body. These interesting properties have made silica nanoparticles the most studied nanoparticle-based PDT systems.
The delivery of photosensitisers embedded in porous silica nanoparticles has many advantages: almost any type of photosensitiser can be used. Second, the concentration of photosensitiser can be modulated as needed increasing or decreasing it.
When the photosensitisers are incorporated on to silica nanoparticles trough covalent bonds, it is possible sarcoma cancer research uk avoid the eventual release of the compounds in the media, and the consequent lost of sarcoma cancer research uk or the appearance of side effects.
Gold nanoparticles: Gold nanoparticles have been targeted to breast cancer cells by incorporating a primary antibody to the ir surface in addition to a zinc phthalocyanine photosensitiser and a bioavailability and solubility enhancer, with promising results [ 5051 ]. Gold particles with various diameters and uniform size distribution have been demonstrated to have novel and fascinating properties. The goal of the synthesis methods is to produce size controllable gold nanoparticles.
Many methods are based on the reduction of tetrachloric acid HAuCl4 to form gold nanoparticles.
The formation and stabilization of nanosized colloidal metal particles demands careful attention to the preparation conditions and to the presence of stabilizers. Nanoparticles virus de papiloma en la boca sintomas silver, gold, platinum, and copper have been prepared by various methods, but most of their shapes have been limited to spheres [ 5253 ].
Papillon zeugma luxury nanoparticles: The magnetic nanoparticles offer the possibility of being directed towards a specific target in the human sarcoma cancer research uk and remaining eventually localised, by means of an applied magnetic field. Iron coated nanoparticles are therefore appropriate to be used as magnetic carriers of medical drugs, magnetic resonance imaging contrasts, biological labels etc, adsorbed into the carbon surface.
As one of the most important materials, magnetite Fe3O4 nanoparticles have attracted a lot of attentions for their interesting magnetic properties and potential applications in the fields of biology, pharmacy and diagnostics [ 54 ].
The magnetite Fe3O4 with oleic acid nanoparticles analyzed by TEM showed a spherical shape with a narrow size distribution. Figure 3.
The general trend in current research from nanomedicine is the application use of photosensitizers for PDT by development of photoactive nanoparticles and to modify photosensitizers to improve effect of photodynamic therapy.
PS can be modified by encapsulated them in delivery agents such as liposomes [ 93 ], micelles [ 81 ], ceramic based nanoparticles [ 49 ], and polymer nanoparticles [ 5767 sarcoma cancer research uk. Some examplification will be shown bellow.