Translation of photodynamic therapy and photodiagnostics into the clinic: Status and obstacles

Rühm, Adrian; Wang, Xuili; Lilge, Lothar

doi:10.1002/tbio.202380001

Cited by 1 publication

(2 citation statements)

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“…PDT involves the use of a photosensitizer that under light irradiation reaches the excited state and transfers energy to the surrounding oxygen-generating radicals that in turn oxidize nucleic acids, proteins, and phospholipids. , This cascade finally leads to cellular damage up to death. 5-ALA is the precursor of the synthesis of the endogenous photosensitizer Protoporphyrin IX; it is currently used in dermatology and for the treatment of accessible skin cancers. ,, One of the main limitations of 5-ALA, a hydrophilic zwitterion, is the poor penetration through the hydrophobic layers of skin .…”

Section: Discussionmentioning

confidence: 99%

“…A more innovative treatment of nonmetastatic melanoma is photodynamic therapy (PDT). , PDT is a minimally invasive medical treatment with the advantages of high selectivity and direct access to the target area (melanoma cells) with almost no side effects . This approach is based on the use of a photosensitizer that is administered topically and selectively concentrated around the malignant tissue; when irradiated by a light with an appropriate and specific wavelength, the photosensitizer is activated and can produce cytotoxic reactive oxygen species (ROS).…”

Section: Introductionmentioning

confidence: 99%

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Enhanced Delivery of 5-Aminolevulinic Acid by Lecithin Invasomes in 3D Melanoma Cancer Model

Gaballo,

Ragusa,

Nobile

et al. 2023

Mol. Pharmaceutics

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Photodynamic therapy (PDT) is a noninvasive therapeutic approach for the treatment of skin cancer and diseases. 5-Aminolevulinic acid is a prodrug clinically approved for PDT. Once internalized by cancer cells, it is rapidly metabolized to the photosensitizer protoporphyrin IX, which under the proper light irradiation, stimulates the deleterious reactive oxygen species (ROS) production and leads to cell death. The high hydrophilicity of 5-aminolevulinic acid limits its capability to cross the epidermis. Lipophilic derivatives of 5-aminolevulinic acid only partly improved skin penetration, thus making its incorporation into nanocarriers necessary. Here we have developed and characterized 5-aminolevulinic acid loaded invasomes made of egg lecithin, either 1,2-dilauroyl-sn-glycero-3-phosphocholine or 1,2-dioleoyl-sn-glycero-3-phosphocholine, and the terpene limonene. The obtained invasomes are highly thermostable and display a spherical morphology with an average size of 150 nm and an encapsulation efficiency of 80%; moreover, the ex vivo epidermis diffusion tests established that nanovesicles containing the terpene led to a much higher skin penetration (up to 80% in 3 h) compared to those without limonene and to the free fluorescent tracer (less than 50%). Finally, in vitro studies with 2D and 3D human cell models of melanoma proved the biocompatibility of invasomes, the enhanced intracellular transport of 5-aminolevulinic acid, its ability to generate ROS upon irradiation, and consequently, its antiproliferative effect. A simplified scaffold-based 3D skin model containing melanoma spheroids was also prepared. Considering the results obtained, we conclude that the lecithin invasomes loaded with 5-aminolevulinic acid have a good therapeutic potential and may represent an efficient tool that can be considered a valid alternative in the topical treatment of melanoma and other skin diseases.

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