Highly Effective Dual-Function Near-Infrared (NIR) Photosensitizer for Fluorescence Imaging and Photodynamic Therapy (PDT) of Cancer

We
report herein the synthesis and biological efficacy of near-infrared
(NIR), bacteriochlorin analogues: 3-(1′-butyloxy)­ethyl-3-deacetyl-bacteriopurpurin-18-N-butylimide methyl ester (3) and the corresponding
carboxylic acid 10. In in vitro assays, compared to its
methyl ester analogue 3, the corresponding carboxylic
acid derivative 10 showed higher photosensitizing efficacy.
However, due to drastically different pharmacokinetics in vivo, the
PS 3 (HPLC purity >99%) showed higher tumor uptake
and
long-term tumor cure than 10 (HPLC purity >96.5%)
in
BALB/c mice bearing Colon 26 tumors. Isomerically pure R- and S- isomers of 3 (3a and 3b, purity by HPLC > 99%) under similar treatment
parameters showed identical efficacy in vitro and in vivo. In addition,
photosensitizer (PS) 3 showed limited skin phototoxicity
and provides an additional advantage over the clinically approved
chemically complex hematoporphyrin derivative as well as other porphyrin-based
PDT agents, which makes 3 a promising dual-function agent
for fluorescence-guided surgery with an option of phototherapy of
cancer.