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-<i>N</i>-butylimide methyl ester (<b>3</b>) and the corresponding carboxylic acid <b>10</b>. In in vitro assays, compared to its methyl ester analogue <b>3</b>, the corresponding carboxylic acid derivative <b>10</b> showed higher photosensitizing efficacy. However, due to drastically different pharmacokinetics in vivo, the PS <b>3</b> (HPLC purity >99%) showed higher tumor uptake and long-term tumor cure than <b>10</b> (HPLC purity >96.5%) in BALB/c mice bearing Colon 26 tumors. Isomerically pure <i>R</i>- and <i>S</i>- isomers of <b>3</b> (<b>3a</b> and <b>3b</b>, purity by HPLC > 99%) under similar treatment parameters showed identical efficacy in vitro and in vivo. In addition, photosensitizer (PS) <b>3</b> 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 <b>3</b> a promising dual-function agent for fluorescence-guided surgery with an option of phototherapy of cancer

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-<i>N</i>-butylimide methyl ester (<b>3</b>) and the corresponding carboxylic acid <b>10</b>. In in vitro assays, compared to its methyl ester analogue <b>3</b>, the corresponding carboxylic acid derivative <b>10</b> showed higher photosensitizing efficacy. However, due to drastically different pharmacokinetics in vivo, the PS <b>3</b> (HPLC purity >99%) showed higher tumor uptake and long-term tumor cure than <b>10</b> (HPLC purity >96.5%) in BALB/c mice bearing Colon 26 tumors. Isomerically pure <i>R</i>- and <i>S</i>- isomers of <b>3</b> (<b>3a</b> and <b>3b</b>, purity by HPLC > 99%) under similar treatment parameters showed identical efficacy in vitro and in vivo. In addition, photosensitizer (PS) <b>3</b> 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 <b>3</b> a promising dual-function agent for fluorescence-guided surgery with an option of phototherapy of cancer

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-<i>N</i>-butylimide methyl ester (<b>3</b>) and the corresponding carboxylic acid <b>10</b>. In in vitro assays, compared to its methyl ester analogue <b>3</b>, the corresponding carboxylic acid derivative <b>10</b> showed higher photosensitizing efficacy. However, due to drastically different pharmacokinetics in vivo, the PS <b>3</b> (HPLC purity >99%) showed higher tumor uptake and long-term tumor cure than <b>10</b> (HPLC purity >96.5%) in BALB/c mice bearing Colon 26 tumors. Isomerically pure <i>R</i>- and <i>S</i>- isomers of <b>3</b> (<b>3a</b> and <b>3b</b>, purity by HPLC > 99%) under similar treatment parameters showed identical efficacy in vitro and in vivo. In addition, photosensitizer (PS) <b>3</b> 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 <b>3</b> a promising dual-function agent for fluorescence-guided surgery with an option of phototherapy of cancer