Usher syndrome type IIa (OMIM 276901), an autosomal recessive disorder characterized by moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa, maps to the long arm of human chromosome 1q41 between markers AFM268ZD1 and AFM144XF2. Three biologically important mutations in Usher syndrome type IIa patients were identified in a gene (USH2A) isolated from this critical region. The USH2A gene encodes a protein with a predicted size of 171.5 kilodaltons that has laminin epidermal growth factor and fibronectin type III motifs; these motifs are most commonly observed in proteins comprising components of the basal lamina and extracellular matrixes and in cell adhesion molecules.

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Potentially, intradermal ALA-PDT using various ALA concentrations may be useful for treating vascular lesions (malformations, hemangiomas, tumors), EG/AG disorders, fat or deep targets in skin.

Antibody-coupled photosensitive molecules can achieve an ideal tumor-specific photodynamic therapy (PDT) and show strong clinical application potential. However, some inherent disadvantages, such as long circulation half-life, poor permeation into solid tumors, and difficulty in obtaining uniform coupling products, present potential problems to clinical applications. In this study, we propose a novel design of targeting photosensitizers, based on a very small targeting protein (an affibody molecule) coupled with photosensitive compounds, to address these problems. In the synthesis, photosensitive pyropheophorbide-a (Pyro) is modified with a PEG linker (molecular weight of 727 Da) and then site specifically coupled to the anti-HER2 Z HER2:2891 affibody protein to provide a homogeneous protein-coupled photosensitizer via a convenient process. In vitro and in vivo experiments show that this molecule has an ideal selectivity for binding and photocytotoxicity against HER2-positive cells (more than 50-fold selectivity between HER2-high expression and HER2-low expression cells) and highly specific tumor accumulation; at a relatively low dose, it effectively eliminated HER2-high expression NCI−N87 tumors in a mouse model. It is worth noting that Pyro only has a moderate photodynamic activity; however, the affibody-coupled Pyro molecule (Pyro-Linker-Z HER2 ) still shows excellent tumor therapeutic function. The more ideal tumor permeability of small ligands may be helpful to enhance the drug concentration in the tumor site and the ability to penetrate deeply inside the tumor. Coupling photosensitive compounds with affibody proteins may provide a new way for targeting PDT of tumors.

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