Figure 19.

Concept design and application of PS fluorescence in site-activated constructs. (A) Release of Ce6 for PFD and PDT following cleavage of a cathepsin-B-specific construct in a subcutaneous murine model for human fibrosarcoma. Three-dimensional fluorescence-mediated tomography was used to image the HT1080 fibrosarcomas following 24 h incubation with a poly-L-lysine-Ce6 construct (0.125 mg Ce6 eq./kg).¹⁵² (B) Proof-of-concept study demonstrating the cleavage of a peptide linker by MMP-7 for PFD and PDT in a subcutaneous murine model for human epidermoid cancer. The PP_MMP7B construct (drug) was injected intravenously (80nmol) in a single mouse bearing two KB tumors on each hind leg. Only one tumor, left leg, was treated and this mouse was monitored by white light and fluorescence imaging before treatment (left image, 3 h after drug injection) and 1 h after PDT (right image, 5 h after drug injection) on one hind flank. Right Image: Treated tumor on the left leg became edematous one hour post PDT while no fluorescence change is observed in untreated right tumor.¹⁵⁴ (C) Mechanism for the cleavage of an enzyme activated prodrug where the blue balls represent the inactive PSs in the uncleaved construct, and the red balls represent the photoactive PSs. The image shows PS fluorescence in cellular co-cultures of S. aureus with human foreskin fibroblasts (HFF) where significantly greater fluorescence intensity is observed in bacterial cells, than in the neighboring fibroblasts indicating cleavage of construct only at the site of infection.¹³ (Figures reproduced with permission from: (A) ref 152; Copyright 2006, American Association for Cancer Research. (B) ref 154; Copyright 2007, The National Academy of Sciences of the USA. (C) ref 13; Copyright 2009, Wiley.)