Photodynamic therapy – hypericin tetraether liposome conjugates and their antitumor and antiangiogenic activity

Abstract

Photodynamic therapy (PDT) is an established noninvasive tumor treatment. The hydrophobic natural occurring pigment hypericin shows a lot of attractive properties for the application in PDT. Hence, the administration to biological systems or patients requires the formulation in drug carriers enabling sufficient bioavailability. Therefore, free hypericin was encapsulated by the thin film hydration method or a hypericin-hydroxypropyl-β-cyclodextrin inclusion complex (Hyp-HPβCD) was incorporated by dehydration-rehydration vesicle method in either conventional or ultra-stable tetraether lipid (TEL) liposomes. The hydrodynamic diameter of the prepared nanoformulations ranged between 127 and 212 nm. These results were confirmed by atomic force microscopy. All liposomes showed a good stability under physiological conditions. TEL liposomes which tend to build more rigid bilayers, generate higher encapsulation efficiencies than their conventional counterparts. Furthermore, the suitability for intravenous application was confirmed by hemocompatibility studies resulting in a hemolytic potential less than 20% and a coagulation time less than 50 sec. The uptake of liposomal hypericin into human ovarian carcinoma cells (SK-OV-3) was confirmed using confocal microscopy and further characterized by pathway studies. It was demonstrated that the lipid composition and intraliposomal hypericin localization influenced the anti-vascular effect in the chorioallantoic membrane (CAM). While hypericin TEL liposomes exhibit substantial destruction of the microvasculature drug-in-cyclodextrin TEL liposomes showed no effect. Nevertheless, both formulations yielded severe photocytotoxicity in SK-OV-3 cells in a therapeutic dosage range. Conclusively, hypericin TEL liposomes would be perfectly suited for anti-vascular targeting while Hyp-HPβCD TEL liposomes could deliver the photosensitizer to the tumor site in a more protected manner.

Photodynamic Therapy of Ovarian Carcinoma Cells with Curcumin-Loaded Biodegradable Polymeric Nanoparticles

“…Various concentrations of CUR-NP and free curcumin (dissolved in DMSO) were added to the wells and incubated for 4 h. Irradiation was performed at a wavelength of 457 nm with a radiation fluence of 8.6 J/cm 2 and the plates were incubated overnight. Dark (un-irradiated) plates were used as control [39]. Subsequently, the medium was replaced with fresh medium containing MTT dye and cells were incubated for 4 h. Absorbance of the resulting formazan crystals dissolved in DMSO was measured using a plate reader (FLUOstar Optima; BMG Labtech, Offenburg, Germany) at 570 nm.…”

Enhancing Breast Cancer Treatment Using a Combination of Cannabidiol and Gold Nanoparticles for Photodynamic Therapy

“…Hypericin can cause cancer cell death via the apoptotic pathway, autophagy or the necrotic pathway, which renders it an ideal PS of choice. It is rapidly removed by normal healthy cells and, hence, can be used as a fluorescent marker for diagnostic imaging [33,34,35]. However, because of its hydrophobicity, it is almost impossible to apply therapeutic doses of Hypericin [21,36].…”

Application of nanotechnology for enhancing photodynamic therapy via ameliorating, neglecting, or exploiting tumor hypoxia

“…Several molecular abnormities in TME have been the target for regulating tumor hypoxia. For example, in contrast to the “heating” strategy discussed in the preceding section, anti‐angiogenic treatment is also a promising strategy to normalize the tumor microvasculature and thus increase the intratumoral blood perfusion 25 . As we know, upon PDT treatment, the tumor microvasculature rapidly shuts down partially or entirely, resulting in blood flow stasis and fast depletion of the local oxygen supply 26 .…”