Photophysical properties of <font>Zn</font>(<font>II</font>) phthalocyaninates incorporated into liposomes

Rodriguez, Myriam E.; Awruch, Josefina; Dicelio, Lelia E.

doi:10.1142/s1088424602000166

Cited by 28 publications

(35 citation statements)

References 20 publications

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“…The increase in fluorescence continues with progressive increase in polymer concentration until saturation when Pc 4 is in its maximum equilibrium association state with the hydrophobic PCL core of the micelles. 6 From the spectrofluorometric data, the equilibrium association constant was determined using Eq. (1) which was reported by Rodriguez et al…”

Section: Pc 4 Encapsulation and Determination Of Association Constantmentioning

confidence: 99%

“…Active research in this area is evident from reports of (a) encapsulation of PS molecules in liposomes, [6][7][8][9] dendrimers, 10,11 micelles [12][13][14][15] and polymeric nanoparticles, 16-21 (b) conjugation of PS molecules to gold nanoparticles 22 and other inorganic nanoparticles, [23][24][25][26] and (c) engineering of a cell-selective delivery strategy of the nanoparticles or PS molecules themselves using tumor-homing motifs like albumin, transferrin, LDL, monoclonal antibodies and folic acid. 6,[27][28][29] Following this rationale, we are investigating the formulation of a PS, Pc 4, in biocompatible micelles from a polyethylene glycol-block-poly-e-caprolactone (PEG-PCL) block copolymer. Pc 4 ( Fig.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Delivery of the photosensitizer Pc 4 in PEG–PCL micelles for in vitro PDT studies

Master

Rodriguez

Kenney

et al. 2010

Journal of Pharmaceutical Sciences

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163

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Section: Pc 4 Encapsulation and Determination Of Association Constantmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Delivery of the photosensitizer Pc 4 in PEG–PCL micelles for in vitro PDT studies

Master

Rodriguez

Kenney

et al. 2010

Journal of Pharmaceutical Sciences

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163

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“…[1][2][3][4][5][6][7][8][9] Such formulations, unfortunately, are developed mostly on an empirical basis, and systematic quantitative studies on the potential of a given formulation to solubilize a drug are lacking. The incorporation of 20-S-(+)-camptothecin (CPT) into liposomes is described in the literature mostly in a qualitative manner, 10 and the few quantitative data are difficult to compare because of the differences in their experimental approaches.…”

Section: Introductionmentioning

confidence: 99%

A method to determine the incorporation capacity of camptothecin in liposomes

2004

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The purpose of this study was to establish a new experimental approach to determine the maximum amount of camptothecin (CPT) that can be incorporated in liposomes, and to use this method to compare the CPT-incorporation capacity of various liposome formulations. Small, CPT-saturated liposomes were prepared by dispersing freeze-dried blends of lipids and drug in phosphate buffer, and subsequent probe-sonication. Excess precipitated CPT could be separated from the liposomes by ultracentrifugation. The small and homogeneous liposome size obtained gave a good and reproducible recovery of liposomes in the supernatant (>80%), whereas the acidic pH (pH 6.0) kept CPT in its hydrophobic lactone form, which is poorly soluble in the buffer. The maximum CPT-incorporation capacity of 12 different liposome formulations was investigated, using the described method, and was found to vary widely. With liposomes made of neutral and anionic phospholipids, the solubility of CPT in the buffer was improved by approximately a factor of 10 (from ~2.7 to 15-50 µg/mL) as compared with buffer. With cationic liposomes containing 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), a maximum CPT-solubilization of ~100-fold, the buffer solubility was reached, probably owing to an electrostatic interaction between the cationic lipids and the carboxylate-CPT isomer. Increasing DOTAP fractions within egg-phosphatidylcholine (EPC)/DOTAP liposomes reached a CPT-incorporation plateau at ~20 mol% DOTAP. The presented approach appears suitable to study the incorporation capacity of any drug component within small vesicles as long as the liposome incorporation is high relative to the intrinsic water solubility of the drug.

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“…The fluorescence increases with additional liposomes until a maximum fluorescence intensity is reached, at which point Pc 4 is maximally monomerized. The blue-shift of the fluorescence spectra for Pc 4 is typical of the change in shape of spectra for other phthalocyanines upon addition of lipid [25]. The shape of the emission spectra is the same in PBS and in liposomal suspension, indicating that the monomer fluorescence specie is the same (Fig.…”

Section: Determination Of Binding Constants Of Pc 4 To Liposomesmentioning

confidence: 72%

“…Only Pc 4 monomers bind to liposomes and become fluorescent. Association constants for Pc 4 were calculated using equation 1 [25]:…”

Section: Binding Of Pc 4 and Nao To Liposomesmentioning

confidence: 99%

Initial targets and cellular responses to PDT

et al. 2007

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Pc 4, a photosensitizer first synthesized at Case Western Reserve University and now in clinical trial at University Hospitals of Cleveland, has been shown to bind preferentially and with high affinity to mitochondrial and endoplasmic reticulum membranes. Upon photoirradiation of Pc 4-loaded cells, membrane components are photodamaged. In most cancer cells, apoptosis is triggered by the initial photodamage; however, in cells deficient in one of the critical intermediates of apoptosis, this process does not occur, although the cells remain as sensitive to the lethal effects of Pc 4-PDT as the apoptosis-competent cells, when cell death is determined by colony formation. Here we report that an alternative death process, autophagy, is induced in all cells tested and becomes the dominant pathway for elimination of lethally damaged cells when apoptosis is compromised. The anti-apoptotic protein Bcl-2, when overexpressed, protects only apoptosis-competent cells against loss of clonogenicity, while the autophagy inhibitor 3-methyladenine provides a markedly greater protection to apoptosis-deficient cells. The results suggest that the primary determinant of cell death is not the final pathway for elimination of the cells but the initial photodamage to critical membrane targets. In attempts to identify those targets, we have studied the role of different membrane phospholipids in the localization of Pc 4. Cardiolipin (CL) is a phospholipid found exclusively in the mitochondrial inner membrane and at the contact sites between the inner and outer membranes. Previous fluorescence resonance energy transfer studies revealed colocalization of Pc 4 and CL, which points to CL as a possible binding site and target for Pc 4. Unilamellar liposomes with different lipid compositions were used as membrane models to test the affinity of Pc 4. As revealed by the binding constants, Pc 4 does not display preferential binding to CL in these systems. Moreover, binding affinities appear to be independent of lipid composition. Localization of Pc 4 in mitochondrial membranes is likely determined by proteins or other factors not replicated in the liposomes. Studies in cells with modified CL content could report modified binding affinities.

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Photophysical properties of Zn(II) phthalocyaninates incorporated into liposomes

Cited by 28 publications

References 20 publications

Delivery of the photosensitizer Pc 4 in PEG–PCL micelles for in vitro PDT studies

Delivery of the photosensitizer Pc 4 in PEG–PCL micelles for in vitro PDT studies

A method to determine the incorporation capacity of camptothecin in liposomes

Initial targets and cellular responses to PDT

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