Unusual Photoinduced Response of mTHPC Liposomal Formulation (Foslip)

Abstract

Liposomal formulations of meso-tetra(hydroxyphenyl)chlorin (mTHPC) have already been proposed with the aim to optimize photodynamic therapy. Spectral modifications of these compounds upon irradiation have not yet been investigated. The objective of this study was to evaluate photobleaching properties of mTHPC encapsulated into dipalmitoylphosphatidylcholine (DPPC) liposomes, Foslip. Fluorescence measurements in DPPC liposomes with different DPPC:mTHPC ratios demonstrated a dramatic decrease in fluorescence anisotropy with increasing local mTHPC concentration, thus suggesting strong interactions between mTHPC molecules in lipid bulk medium. Exposure of Foslip suspensions to small light doses (<50 mJ/cm(2)) resulted in a substantial drop in fluorescence, which, however, was restored after addition to the sample of a non-ionic surfactant Triton X-100. We attributed this behavior to photoinduced fluorescence quenching. This effect depended strongly on the molar DPPC:mTHPC ratio and was revealed only for high local mTHPC concentrations. The results were interpreted supposing energy migration between closely located mTHPC molecules with its subsequent dissipation by the molecules of photoproduct acting as excitation energy traps. We further assessed the effect of photoinduced quenching in plasma protein solution. Relatively slow kinetics of photoinduced Foslip response during incubation in the presence of proteins was attributed to mTHPC redistribution from liposomal formulations to proteins. Therefore, changes in mTHPC distribution pattern in biological systems would be consistent with changes in photoinduced quenching and would provide valuable information on mTHPC interactions with a biological environment.

Hypericin- and mTHPC-mediated photodynamic therapy for the treatment of cariogenic bacteria

“…While for cancer PDT light sources with longer wavelengths are preferred because of deeper penetration needs, the superficial sites of cariogenic bacteria are easily accessible with our device. Its wavelength range (400-505 nm) is perfectly suitable for activation of FOS, since the Soret band of this photosensitizer is at 420 nm [32]. The spectrum of HYP contains a very broad absorption band near 460 nm but, notably, main peaks are outside the wavelength range of our lamp [33].…”

Photodynamic therapy with conventional and PEGylated liposomal formulations of mTHPC (temoporfin): comparison of treatment efficacy and distribution characteristics in vivo

“…21 It consists in a significant liposomal mTHPC fluorescence decrease after irradiation of the sample with a very low light dose, which is restored after the destruction of liposomes by a neutral detergent. The mechanism of fluorescence quenching is related to the formation of a small amount of quenchers upon photoirradiation, which are primary nonfluorescent photooxidation products of mTHPC.…”

“…The mechanism of fluorescence quenching is related to the formation of a small amount of quenchers upon photoirradiation, which are primary nonfluorescent photooxidation products of mTHPC. 21 The effect of photoinduced fluorescence quenching arises from energy migration between closely located mTHPC molecules in liposomes, the energy being dissipated by nonfluorescent photoproducts acting as energy traps. After addition of the detergent, the energy migration ceases, and the mTHPC fluorescence of the sample is restored.…”

<italic>In vivo</italic> quantification of photosensitizer concentration using fluorescence differential path-length spectroscopy: influence of photosensitizer formulation and tissue location

“…24 Two liposomal mTHPC formulations that have been developed are Foslip® and Fospeg®. 8,[25][26][27][28][29][30][31][32] In Fospeg, the surfaces of the liposomes are coated by a hydrophilic polymer to further decrease recognition by the RES and thus increase circulation time over Foscan and Foslip. 24,33 Both the incorporation of mTHPC into liposomes and the composition of different liposomes are known to significantly influence the spectral properties.…”

“…24,33 Both the incorporation of mTHPC into liposomes and the composition of different liposomes are known to significantly influence the spectral properties. 28,30 Furthermore, Foslip and Fospeg are known to exhibit different redistribution patterns and liposomal stability in serum. 30 We have therefore also investigated the influence of these nanocarriers on FDPS performance.…”