Rational design of a receptor-targeted photodynamic molecular beacon for the multilevel control of singlet oxygen production and PDT activity in cancer cells

Juan Chen; Klara Stefflova; Mike Warren; Jiachuan Bu; Brian C. Wilson; Gang Zheng

doi:10.1117/12.699754

13 February 2007 Rational design of a receptor-targeted photodynamic molecular beacon for the multilevel control of singlet oxygen production and PDT activity in cancer cells

Juan Chen, Klara Stefflova, Mike Warren, Jiachuan Bu, Brian C. Wilson, Gang Zheng

Author Affiliations +

Proceedings Volume 6449, Genetically Engineered and Optical Probes for Biomedical Applications IV; 644906 (2007) https://doi.org/10.1117/12.699754
Event: SPIE BiOS, 2007, San Jose, California, United States

Abstract

Photodynamic therapy (PDT) involves the combined action of light, oxygen and a photosensitizer (PS). It offers unique control in the PS's action because the key cytotoxic agent, singlet oxygen (¹O₂), is only produced in situ upon irradiation. The ¹O₂ production can be controlled in three levels. The first level involves the judicious use of fiber optics to selectively deliver light to disease tissues. The second level is to exert control over the PS's localization by selectively delivering PS to cancer cells. The third level is to exert control of the PS's ability to generate ¹O₂ in responding to specific cancer biomarkers. Here, we present two PDT agents based on the latter two levels of ¹O₂ control. The first PDT agent "PPF" contains a PS (Pyro) and a tumor homing molecule (folate) and a peptide linker. PPF was found to be selectively accumulated in cancer cells via folate receptor (FR) pathway. The second PDT agent "PP_MMP7B" is a matrix metalloproteinase-7 (MMP7)-triggered photodynamic molecular beacon (PMB) containing a PS (Pyro), a ¹O₂ quencher (BHQ3) and a MMP7-cleavable peptide linker. Thus, the ¹O₂ production of PP_MMP7B is highly sequence-specific and its photodynamic cytotoxicity is MMP7-dependent. Since these agents are designed to share functional modules (PS and peptide linker) and common cancer cell model (KB cells overexpress both FR and MMP7), it forms the basis for rational design of receptor-targeted PMB for achieving a multi-level control of ¹O₂ production in cancer cells, which in term, could provide a much higher level of PDT selectivity.

Citation Download Citation

Juan Chen, Klara Stefflova, Mike Warren, Jiachuan Bu, Brian C. Wilson, and Gang Zheng "Rational design of a receptor-targeted photodynamic molecular beacon for the multilevel control of singlet oxygen production and PDT activity in cancer cells", Proc. SPIE 6449, Genetically Engineered and Optical Probes for Biomedical Applications IV, 644906 (13 February 2007); https://doi.org/10.1117/12.699754

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