Synthesis and biological evaluation of phthalocyanine-peptide conjugate for EGFR-targeted photodynamic therapy and bioimaging

To improve the biocompatibility and tumor selectivity, we employed an epidermal growth factor receptor (EGFR) binding peptide (namely GE11, with a sequence of Tyr-His-Trp-Tyr-Gly-Tyr-Thr-Pro-Gln-Asn-Val-Ile) as a tumor directing vector for the delivery of zinc(II) phthalocyanine for targeted photodynamic therapy and bioimaging. The photophysical properties, cellular uptake, in vitro cytotoxicity, and in vivo biodistribution of this phthalocyanine-peptide conjugate (namely Pc-GE11) have been evaluated. Pc-GE11 exhibited higher cellular uptake on EGFR-overexpressing epidermoid carcinoma A431 cells when compared with that on human breast adenocarcinoma MCF7 cells (low EGFR expression). Moreover, pretreatment of A431 cells with GE11 peptide inhibited the cellular uptake of Pc-GE11 significantly and it exhibited exclusive light-activated cytotoxicity toward A431 cells. Furthermore, Pc-GE11 showed much higher tumor accumulation than the non-targeted control compound containing a random peptide sequence (Tyr-Trp-Gly-Pro-Asn-Ile-His-Tyr-Tyr-Thr-Gln-Val) after intravenous administration in A431-tumor bearing mice, indicating the potential application of this GE11 peptide-conjugated photosensitizer for targeted photodynamic therapy and bioimaging.