Near-Infrared Fluorescent pH Responsive Probe for Targeted Photodynamic Cancer Therapy

Abstract

We developed a pH dependent amino heptamethine cyanine based theranostic probe (I2-IR783-Mpip) that can be activated by near infrared light. I2-IR783-Mpip, in acidic condition, exhibited an intense, broad NIR absorption band (820–950 nm) with high singlet oxygen generation upon exposure to NIR light (~850 nm). Theoretical calculations showed that the protonation of the probe in an acidic environment decreased the molecular orbital energy gaps and increased the intramolecular charge transfer efficiency. I2-IR783-Mpip exhibited good photodynamic efficiency towards liver hepatocellular carcinoma cells under physiological and slightly acidic conditions while normal human embryonic kidney cells remained alive under the same conditions. Detection of intracellular reactive oxygen species (ROS) in cells treated with I2-IR783-Mpip after NIR light exposure confirmed PDT efficiency of the probe in acidic environment. Moreover, I2-IR783-Mpip also demonstrated efficient phototoxicity under deep-seated tumour cell system. We believed this is the first PDT agent that possesses intrinsic tumour binding and selectively eradicate tumour in acidic environment under 850 nm NIR lamp.

Explorations into the Effect of meso‐Substituents in Tricarbocyanine Dyes: A Path to Diverse Biomolecular Probes and Materials

“…The use of compounds already established for NIR‐I imaging could significantly ease the establishment of imaging in the NIR‐II window [63–64] . Likewise, further development of cyanine dyes for applications such as PDT is of great interest, due to the penetration depth of light in the NIR window and their high molar absorptivity [3b, 41, 43, 65] …”

“…Examples include a sphingosine derivative (an amino alcohol, and a primary part of sphingolipids, which make up parts of the cell membrane), [34] photocleavable prodrugs such as tamoxifen‐like compounds, [38] (PEG)ylated derivatives such as those reported by Lu et al., [39] ratiometric probes for nitroreductase, [40] and agents for photodynamic therapy, as reported by Jiao et al [41] . Alternative strategies also include pH cleavable prodrugs, as reported by Xing et al., [42] and pH activated agents for photodynamic therapy [43] …”

Expanded porphyrins: functional photoacoustic imaging agents that operate in the NIR-II region

“…Cancer broadly speaking represents another area where monitoring pH via PAI could be beneficial in the context of diagnostic and therapeutic applications. 8,36 It is well-known that the extracellular tumor microenvironment is slightly acidic 6.4 -7.0. 37 Most cancer environments are also highly reducing.…”

Rapid Clearance of IR783 and Methyl‐β‐cyclodextrin Complex for Improved Tumor Imaging

“…[ 13–15 ] Among the tumor‐targeted NIR fluorophores, IR783 has been widely used for tumor‐targeted imaging owing to its high water solubility, low cytotoxicity, and tumor‐targeting specificity. [ 16–19 ] Despite these potential advantages of IR783, nonspecific uptake in normal tissues/organs and slow clearance from the body until 80 h post‐injection have been reported, which are major challenges to achieve a sufficient TBR for the accurate tumor imaging. [ 14,15 ] In this regard, the molecular design of IR783 for improved biodistribution and clearance that maintain tumor targetability but also enhance TBR through a rapid clearance in vivo is still highly needed.…”