A biotin receptor-targeted silicon(IV) phthalocyanine for in vivo tumor imaging and photodynamic therapy.

Phthalocyanines (Pcs) are a kind of potential photosensitizers for fluorescence imaging and photodynamic therapy (PDT). However, the clinical application of Pcs is suffered from their poor solubility, high aggregation tendency and low tumor-specificity. To address these problems, two biotin moieties were linked to the axial positions of silicon(IV) phthalocyanine (SiPc) through hydrophilic polyethylene glycol (PEG) linkers to synthesize a new water-soluble and tumor-targeting photosensitizer (compound 1). The introduction of PEG linkers on SiPc markedly reduced the aggregation tendency of the conjugate. In vitro assays also proved that compound 1 could specifically accumulate in biotin receptor (BR) positive Hela cells through the BR-mediated internalization. Owing to the good characteristics of water-solubility and low aggregation, the bioactivity of compound 1 was examined in the xenograft tumor model. In vivo imaging and tissue distribution studies showed that compound 1 selectively accumulated in the tumor tissue, with tolerable signals found in other organs of the tumor-bearing mice. Furthermore, compound 1 could significantly depress tumor progression in vivo under irradiation. After 14 days of the treatment, the tumor volumes were even smaller than the beginning size. All these results reveal that compound 1 is a promising candidate, with low aggregation tendency, high tumor-specificity and water-solubility, for in vivo tumor diagnosis and PDT treatment.