Nanotechnology-Based Photodynamic Therapy for Neovascular Disease Using a Supramolecular Nanocarrier Loaded with a Dendritic Photosensitizer

Abstract

Photodynamic therapy (PDT) for exudative age-related macular degeneration (AMD) was evaluated using a supramolecular nanomedical device, that is, a novel dendritic photosensitizer (DP) encapsulated by a polymeric micelle formulation. The characteristic dendritic structure of the DP prevents aggregation of its core sensitizer, thereby inducing a highly effective photochemical reaction. With its highly selective accumulation on choroidal neovascularization (CNV) lesions, this treatment resulted in a remarkably efficacious CNV occlusion with minimal unfavorable phototoxicity.

Nanodrug applications in photodynamic therapy

“…By now, most of these nanostrategies are used in many areas of PDT. For example, dendrimer porphyrin encapsulation into polymeric micelles [58] is used for the treatment of corneal neovascularization, a major sight-threatening condition caused by inflammation, infections and degenerative disorders [69,70,71]. Visudyne ® the first photodynamic drug approved for treatment of age related macular degeneration (AMD) is used to reduce the risk of vision loss.…”

Dendrimer porphyrin-based self-assembled nano-devices for biomedical applications

“…When the laser irradiation was performed after 15 min of the DP-loaded micelle injection, 78% of fluorescein leakage in the CNV lesions was blocked after 1 day of PDT. 39 More importantly, no macroscopic photodamage was observed on the skin when the rats were exposed to broadband visible light after 4 h of the DP-loaded micelles injection (a Xenon lamp equipped with a 377 to 700 nm bandpass filter with power of 30 mW cm À2 ). In sharp contrast, administering Photofrin, a conventional PS, has resulted in severe skin burns under the same conditions, indicating that DP-loaded micelles may not be hypersensitive to light exposure.…”

“…38 PDT was performed using DP-loaded PIC micelles in an AMD model. 39 After 7 days of photocoagulation in rats, 400 ml of DP-loaded PIC micelles or free DP (including 1.5 mg ml À1 of DP) was administered by tail vein injection. 39 When DP fluorescence was observed in the eyes, DPloaded micelles effectively and selectively accumulated in the CNV lesions.…”

“…39 After 7 days of photocoagulation in rats, 400 ml of DP-loaded PIC micelles or free DP (including 1.5 mg ml À1 of DP) was administered by tail vein injection. 39 When DP fluorescence was observed in the eyes, DPloaded micelles effectively and selectively accumulated in the CNV lesions. The selective accumulation of DP-loaded micelles indicates that the CNV lesions may have features similar to solid tumor vasculatures, such as hyperpermeability and impaired lymphatic Oxygen depletion profiles by free DP (-) and the DP-loaded PIC micelle (-) in PBS containing 10% FBS.…”

Ophthalmic light sensitive nanocarrier systems

“…The framework of ionic dendritic porphyrin prevents the aggregation of porphyrin and ensures effective production of singlet oxygen, even in extremely high concentrations. In general, photosensitizers exhibit large π-conjugation domains and hydrophobic characteristics, causing them to aggregate easily [19]. When photosensitizers are loaded into delivery systems, aggregates form and result in self-quenching of the excited state, which may change the photochemical reaction mechanism from type II to type I.…”