cRGD Peptide-Conjugated Pyropheophorbide-a Photosensitizers for Tumor Targeting in Photodynamic Therapy

• DOI: 10.1021/acs.molpharmaceut.7b01064
• Publication Date: 2018-03-05T06:13:17Z
• Authors: Wenjing Li; Sihai Tan; Yutong Xing; Qian Liu; Shuang Li; Qingle Chen; Min Yu; Fengwei Wang; Zhangyong Hong
• Keywords: Linker; Conjugate

Pyropheophorbide-a (Pyro) is a highly promising photosensitizer for tumor photodynamic therapy (PDT), although its very limited tumor-accumulation ability seriously restricts clinical applications. A higher accumulation of photosensitizers important the treatment deeply seated and larger tumors. The conjugation Pyro with tumor-homing peptide ligands could be useful strategy to optimize physical properties Pyro. Herein, we reported our studies on cyclic cRGDfK (cRGD) peptide, an integrin binding sequence, develop tumor-specific PDT application. To further reduce nonspecific uptake and, thus, background distribution conjugates in normal tissues, opted add hydrophilic polyethylene glycol (PEG) chain extra strongly carboxylic acid group as linker avoid direct connection hydrophobic macrocycle cRGD ligand. We here synthesis characterization these conjugates, influence modification biological function was carefully studied. photodynamic-induced cell-killing were evaluated through both vitro cell-based experiment vivo experiments tumor-bearing mice. Thus, synthesized conjugate significantly improved enrichment selectivity Pyro, well abolished xenograft tumors murine model one-time treatment.