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

Abstract

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.

Chemistry in the Bioactivity of Chlorophylls: An Overview

“…The strategy is the conjugation of a tumor-avid porphyrin and other compound to obtain both effects at the same time. The detection is made using the fluorescence characteristics of porphyrins [120], magnetic resonance or nuclear imaging [121].…”

Synthesis, Characterization and Photodynamic Activity against Bladder Cancer Cells of Novel Triazole-Porphyrin Derivatives

“…These compounds are considered to be highly relevant in the medicinal field due to their high ability to act as photosensitizers in photodynamic therapy (PDT) [4]. In fact, porphyrins and analogues are special candidates for the management of oncological diseases by following the PDT therapy [5][6][7][8][9][10][11][12][13]. PDT is centered in a photooxidation process occurring in target tissues through three key components: photosensitizer (PS), oxygen, and light (sources emitting within the absorption spectrum of the PS) [14].…”

Alkane Chain‐extended Pterin Through a Pendent Carboxylic Acid Acts as Triple Functioning Fluorophore, 1O2 Sensitizer and Membrane Binder

“…Over the past 6-8 years, "smart" compounds that possess dual fluorescence sensing and singlet oxygen sensitizing properties have become a hot topic (14)(15)(16), with success reported in dual function image-guided and photodynamic therapy applications (PDT) (17)(18)(19)(20)(21)(22)(23)(24)(25). Indeed, our previous Oand N-decyl-pterins possessed good singlet oxygen quantum yields (Φ Δ ), but had poor fluorescence quantum yields (Φ F ) some 4-30 fold less compared to native pterin, thereby fulfilling only two of three facets, even though a minor fluorescence increase was observed when intercalated in the membrane (10).…”