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

Abstract

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.

• Authors: Ke Li, Wenyi Dong, Qingzhu Liu, Gaochao Lv, Minhao Xie, Xinchen Sun, Ling Qiu, Jianguo Lin
• Journal: Journal of photochemistry and photobiology. B, Biology (J Photochem Photobiol B) Vol. 190 Pg. 1-7 (Jan 2019) ISSN: 1873-2682 [Electronic] Switzerland
• PMID: 30453160 (Publication Type: Journal Article)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• Cross-Linking Reagents
• Indoles
• Isoindoles
• Organosilicon Compounds
• Photosensitizing Agents
• Receptors, Growth Factor
• biotin receptor
• Polyethylene Glycols
• Biotin
• phthalocyanine

Topics

• Animals
• Biotin (chemistry)
• Cross-Linking Reagents (chemistry)
• HeLa Cells
• Heterografts
• Humans
• Indoles (metabolism, pharmacokinetics, therapeutic use)
• Isoindoles
• Mice
• Neoplasms (diagnostic imaging, therapy)
• Organosilicon Compounds (therapeutic use)
• Photochemotherapy
• Photosensitizing Agents (pharmacokinetics, therapeutic use)
• Polyethylene Glycols (chemistry)
• Receptors, Growth Factor (metabolism)
• Solubility
• Tissue Distribution