The research is devoted to development and study of photosensitizers on a base of injectable nanoparticular formulations of phthalocyanine derivatives absorbing at long wavelength (near-infrared) range of 710–740 nm: Thiosens [liposomal form of aluminum hydroxide 1,8,15,22-tetrakis(phenylsulfanyl)phthalocyanine] and Octasens [polymeric micellar form of zinc 1,4,8,11,15,18,22,25-octachloro-2,3,9,10,16,17,23,24-octakis-(decylsulfanyl)phthalocyanine based on domestic poloxamer Emuxol-268]. Experiments have shown that the photosensitizers under study show high selectivity of accumulation and prolonged retaining at high concentration in tumor, relatively fast clearance from normal tissue and high therapeutic efficiency of photodynamic treatment on model tumors.

The work is devoted to study of new prototype contrasting agents for magnetic resonance imaging on a base of manganese and gadolinium sulphophthalocyanines. Candidate complexes were shown to possess the R1 molar relaxivity values comparable or exceeding ones for commercially available clinical contrast agents such as Magnevist. Intravenous administration of aqueous solution of studied complexes resulted in significant enhancement of contrast of C6 glioma imaging under T1-weighted protocol, allowing to consider them as perspective for further development. Near infrared photosensitizers based on nanoparticular forms of phthalocyanine derivatives.

The possibilities of fl uorescence diagnosis (FD) and photodynamic therapy (PDT) with domestic photosensitizers and domestic equipment in brain tumors have been studied. Investigation of the level and selectivity of accumulation dynamics of Photosens and Tiosens in C6 glioma tissue by spectral fl uorescence method has showed the selective accumulation of both agents in tumor tissue. High effi ciency of PDT with Photosens and Tiosens both as monotherapy and as combined treatment has been shown on the base of pathomorphological criteria. Increase of therapeutic effi cacy of combined treatment of C6 glioma using FD and intraoperative PDT with Alasens has been established.

The possibilities of fl uorescence diagnosis (FD) and photodynamic therapy (PDT) with domestic photosensitizers and domestic equipment in brain tumors have been studied. Investigation of the level and selectivity of accumulation dynamics of Photosens and Tiosens in C6 glioma tissue by spectral fl uorescence method has showed the selective accumulation of both agents in tumor tissue. High effi ciency of PDT with Photosens and Tiosens both as monotherapy and as combined treatment has been shown on the base of pathomorphological criteria. Increase of therapeutic effi cacy of combined treatment of C6 glioma using FD and intraoperative PDT with Alasens has been established.

Size of nanoparticles is one of main factors determining the efficiency of nanostructural antitumor drugs. This work was performed to estimate the influence of liposome size on level and selectivity of photosensitiz er accumulation in tumor and efficiency of photodynamic treatment (PDT) using photosensitizer Tiosens (liposomal form of (PhS)4PcAlOH) with absorption maximum at 720 nm. It was shown that administration of Tiosens dispersions with liposome size range of 75-130 nm results in level and selectivity of photosensitizer accumulation in tumor noticeably higher in comparison to the ones with 180-450 nm size. Liposomes of size less than 50-60 nm show high accumulation both in tumor and normal tissue resulting in less selectivity of accumulation and prolonged retain in normal tissue. PDT using Tiosens dispersion of size below 150 nm causes efficient tumor growth inhibition (TGI) achieving 80%, while use of dispersion of larger liposome size gives only moderate TGI of about 53%.

Conjugates of tetrasulphosubstituted zinc phthalocyanine with rhodamine 6G or rhodamine B have been synthesized and characterized to have four rhodamine 6G or average two rhodamine B residues per phthalocyanine molecule. The ionized conjugates (positive charge on the rhodamine part) are non-soluble in water. Photochemical and photophysical measurements, carried out in dimethylsulphoxide, have shown that the main result of conjugation is efficient intramolecular energy transfer from rhodamine to phthalocyanine part of molecular system. The conjugation results in about twofold decrease of quantum yields for photodegradation, fluorescence and singlet oxygen photogeneration.

A series of conjugates of sulfo- and carboxy-substituted phthalocyanines with rhodamines were prepared, and their electronic absorption and luminescence spectra were studied. An intramolecular transfer of the excitation energy from the rhodamine moiety (donor) to the phthalocyanine moiety (acceptor) was revealed.

The photodynamic activity of dibiotinylated aluminum sulfophthalocyanine was studied in vitro and in vivo. Dibiotinylated aluminum sulfophthalocyanine provided enhanced phototoxic action on OAT-75 cell monolayers as compared with the parent drug. Photodynamic therapy of mice with Ehrlich carcinoma using dibiotinylated aluminum sulfophthalocyanine (0.25mg/kg) resulted in enhanced inhibition of tumor growth, pronounced vascular damage (thrombosis and destruction of vascular walls) and eventual tumor necrosis.

We studied the possibility of using liposomal forms of hydroxyaluminium tetra-3-phenylthiophthalocyanine as a near infrared band photosensitizer. Experiments on mice with solid Ehrlich tumor and subcutaneously transplanted P-388 leukemia revealed high selectivity of accumulation of the photosensitizer in tumors in comparison with normal tissues and high photodynamic activity of the preparation. This photosensitizer can be used as the basis for creating an effective preparation for photodynamic therapy and fluorescent diagnosis.

The importance of singlet oxygen mechanism in photooxidation of phthalocyanine chromophore has been studied for promising singlet oxygen sensitizers: metal-free tetra-tert-butyl phthalocyanine and its Zn , Mg or Al complexes. It has been found that involvement of singlet oxygen in phthalocyanine photodegradation is dependent on the presence and character of the central metal atom, being the most prominent for the metal-free compound and almost negligible for the Al complex. The interaction of dioxygen with metal centers results in a sharp increase of phthalocyanine photooxidation rate.

The reaction of acidic form of the substituted icon phthalocyanine complex (3-PhS- 5-But)4pc′Fe (pc″Fe) with dioxygen in o-dichlorobenzene in the presence of dichloroacetic acid (HX) was investigated. The oxidation of Hpc″FeX gives the corresponding radical cation, which was confirmed by the stoichiometry of reduction of the product formed in this reaction with a two-electron reducing agent. The kinetic equation obtained on the basis of dependences of the oxidation rate on the Hpc″FeX, HX, and O2 concentrations are consistent with the reaction mechanism that implies the formation of a Hpc″FeX complex with O2 and its transformation to give a radical cation under the action of HX.

The photodynamic activity of dibiotinylated aluminium sulphophthalocyanine in vitro and in vivo were studied. It was obtained that in vitro dibiotinylated aluminium sulphophthalocyanine provides the effective damage of small cell lung carcinoma OAT-75. In vivo dibiotinylated aluminium sulphophthalocyanine causes destruction of tumor (Erlich carcinoma), results in total necrosis of tumor tissue and expresses vascular damage (trombosis and destruction of vascular walls) even in concentration 0.25 mg/kg of a body weight.

The influence of sulfonation degree (n) and central atom nature on singlet oxygen quantum yield (ΦΔ) were studied for a series of sulfonated phthalocyanine metal complexes MPcS n mix . It was found that in DMSO, where the studied dyes exist as monomers, ΦΔ values are independent of number and position of the sulfogroups and are equal to 0.11 ± 0.02, 0.19 ± 0.03, 0.37 ± 0.05, 0.38 ± 0.05 and 0.68 ± 0.10 for the metal-free and Mg , Gd , Al and Zn complexes, correspondingly. However, in aqueous solutions, aggregation of the dyes determines their photochemical activity. Substitution in adjacent to macrocycle 3 and 6 benzene positions interferes with aggregation compared to 4 and 5 positions, presumably due to enhanced steric hindrances in the former case. In the ZnPcS n mix series (n varied from 2 to 4), as an example, the linear relationship between degree of aggregation and ΦΔ indicates that only the monomer fraction of the dye is responsible for singlet oxygen production. For less sulfonated samples the order of activity of the dyes in water is as follows: H 2 PcS n mix < M II PcS n mix < M III PcS n mix which is in contrast to their tendencies to form aggregates.

The dependence of the quantum yield of photogeneration of singlet oxygen with aluminum sulfophthalocyanines on the degree of their sulfonation was studied. Experiments showed that Fotosens preparation containing, on the average, about three sulfo groups in the macroring in aqueous buffer solution (pH 7.4) exists in the monomeric form and sensitizes singlet oxygen with a quantum yield ϕΔ 0.42±0.06. Aluminum tetra-4-sulfophthalocyanine forms dimers, and correspondingly ϕΔ is lower: 0.22±0.03. Sulfonated aluminum phthalocyanine containing, on the average, about two sulfo groups in the macroring is aggregated to a significant extent. Addition of Triton X-100 detergent results in partial deaggregation of the dye, and ϕΔ increases from ∼0.01 to 0.15±0.02. In the series including previously unknown aluminum phthalocyanines containing residues of phosphonic acids or their esters, and also aluminum and zinc octacarboxyphthalocyanines, the influence of the dye structure on the quantum yield of generation of singlet oxygen suggests participation of axial hydroxy groups in associate formation. These associates are not manifested spectroscopically and generate singlet oxygen inefficiently. The quantum yields ϕΔ for the monomers and associates are 0.3 and 0.1, respectively.

The synthesis of new metallophthalocyanine-oligonucleotide conjugates is reported. These conjugates can cause sequence-specific photosensitized or catalytic oxidation of DNA by molecular oxygen.

The investigations of photodynamic activity of the dibiotinylated aluminium sulphophthalocyanine in vitro and in vivo were performed. The results obtained showed that in vitro dibiotinylated aluminium sulphophthalocyanine provides an effective damage of small cell lung carcinoma OAT-75. In vivo dibiotinylated aluminium sulphophthalocyanine induces a total damage of Erlich carcinoma with expressed vascular damage (thrombosis and destruction of tumour walls) even in a concentration 0,5 mg/kg of body weight.

Catalytic systems consisting of cobalt phthalocyanine grafted to maleic anhydride-styrene copolymer chemically linked with γ-aminopropylated silochrome have been prepared. In the process of sulfide oxidation with air oxygen the specific catalytic activity of these systems depends strongly on the phthalocyanine concentration in the catalyst. At low phthalocyanine concentrations (below 0.4 × 10−6 mol g−1) the catalytic activity is more than an order of magnitude larger than that of homogeneous catalysts and cobalt phthalocyanine adsorbed on a silochrome surface. The different ways of preparing the catalysts are reflected in the kinetic characteristics of the oxidation process.