Citation: Chen Qingle, Ma Yanhong, Zhao Jisi, Zhao Mei, Li Wenjing, Liu Qian, Xiong Li, Wu Wenjie, Hong Zhangyong. In vitro and in vivo evaluation of improved EGFR targeting peptide-conjugated phthalocyanine photosensitizers for tumor photodynamic therapy[J]. Chinese Chemical Letters, ;2018, 29(7): 1171-1178. doi: 10.1016/j.cclet.2018.04.025 shu

In vitro and in vivo evaluation of improved EGFR targeting peptide-conjugated phthalocyanine photosensitizers for tumor photodynamic therapy

Chen Qingle ^a,b,1 ,
Ma Yanhong ^b,1 ,
Zhao Jisi ^b ,
Zhao Mei ^b ,
Li Wenjing ^b ,
Liu Qian ^b ,
Xiong Li ^c,, ,
Wu Wenjie ^a,, ,
Hong Zhangyong ^b,,

a.
College of Materials Science and Chemical Engineering, Tianjin University of Science and Technology, Tianjin 300457, China
b.
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, College of Life Sciences, Nankai University, Tianjin 300071, China
c.
Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China

Corresponding author: Xiong Li, lixionghn@163.com Wu Wenjie, wwjie@tust.edu.cn Hong Zhangyong, hongzy@nankai.edu.cn

Received Date: 28 February 2018
Revised Date: 13 April 2018
Accepted Date: 18 April 2018
Available Online: 24 July 2018

Figures(9)

Phthalocyanine (Pc) is one of the most promising photosensitizer candidates because of its strong absorption (extinction coefficient ε > 10⁵ L mol^-1 cm^-1) at long wavelengths and strong singlet oxygen generation abilities (a singlet oxygen quantum yield of approximately 50%). However, low tumor targeting, low water solubility and a high tendency to aggregate appear to significantly restrict the compound's application in tumor treatment. Conjugating Pc with peptide ligands could be a useful strategy for alleviating these problems. Here, to further optimize the structures of peptide-conjugated zinc Pcs for PDT therapy, we finely tuned the hydrophilicity of the modified Pc aromatic macrocycle with varied length of polyethylene glycol (PEG) and added an extra PEG linker and an extra glutamic acid between the Pc ring and the peptide ligand to reduce the influence of the ligand on the Pc aromatic ring. Among the synthesized conjugates, Pc-3 showed greatly improved targeting towards tumors and abolished inoculated tumors with only a single PDT treatment in a subcutaneous xenograft tumor model, making this approach a promising therapeutic agent for the treatment of cancer.
- Photodynamic therapy,
- Potosensitizer,
- Phthalocyanine,
- Peptide conjugate
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