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Synthesis, Spectroscopic and Fibroblast Activation Protein (FAP)‐Responsive Properties of Phthalocyanine‐Doxorubicin Conjugates
Author(s) -
Peng XiaoHui,
Chen ShaoFang,
Xu CaiHong,
Zheng BiYuan,
Ke MeiRong,
Huang JianDong
Publication year - 2018
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201800062
Subject(s) - linker , conjugate , chemistry , conjugated system , doxorubicin , phthalocyanine , combinatorial chemistry , stereochemistry , organic chemistry , polymer , medicine , mathematical analysis , mathematics , surgery , chemotherapy , computer science , operating system
Abstract A series of novel phthalocyanine‐doxorubicin (Pc‐DOX) conjugates have been prepared with a fibroblast activation protein (FAP)‐sensitive linker of glycine‐proline (Gly‐Pro) dipeptide. Meanwhile, two Pc‐DOX conjugates ( 1 c and 3 c ) without FAP‐sensitive linker have also been prepared for comparison. For Pc‐DOX conjugates, the photosensitizing properties of the phthalocyanines are partly quenched after being conjugated with DOX. The aggregation behavior of these conjugates is less affected by the surfactant of Cremophor EL compared with that of corresponding precursors in aqueous media. The FAP‐responsive properties have been demonstrated by HPLC analysis and fluorescence spectroscopy in phosphate buffered saline. The Pc‐Gly‐Pro‐DOX conjugate 2 b with longer linker is more sensitive to FAP than the other two Pc‐Gly‐Pro‐DOX conjugates ( 1 b and 3 b ). The results suggest that the longer linker and smaller steric hindrance between phthalocyanine and Dox units are beneficial for the cleavage of Gly‐Pro linker induced by FAP, while the axial or peripheral substituted positions hardly allow the enzymolysis of FAP. This work can thus provide a valuable reference for the targeted chemo‐photodynamic therapy of cancer.