pH-Sensitive and Lysosome Targetable Photosensitizers Based on BODIPYs.

Photodynamic therapy (PDT) is an effective and U.S. Food and Drug Administration (FDA) approved treatment for cancer and other diseases. Photosensitizer is one of the three key components that harvest the energy of light at a certain wavelength. Compared to the conventional fluorophores used as photosensitizers, boron dipyrromethene (BODIPY) derivatives have grown fast in recent years due to their low dark toxicity, versatile tunable sites, and easiness of being paired with other treatments. In this paper, two pH-sensitive BODIPY-based photosensitizers (BDC and BDBrC) were synthesized by adding carbazole moieties onto the BODIPY cores (BD and BDBr) through condensation reactions. BDBrC has two Br atoms at the BODIPY core that promote singlet oxygen generation and further red-shift the absorption maximum peak. Both compounds showed sensitivity toward pH change and generated more singlet oxygen under acidic conditions. The cellular uptake and cell imaging experiments showed that BDBrC can selectively target the lysosome organelle. The further dark cell viability and light cytotoxicity indicate the light triggered PDT treatment can be accomplished with BDBrC.

Mitochondria Penetrating Peptide-Conjugated TAMRA for Live-Cell Long-Term Tracking.

Mitochondria are essential targets for treatment of diseases with mitochondrial disorders such as diabetes, cancer, and cardiovascular and neurodegenerative diseases. Mitochondria penetrating peptides (MPPs) are composed of cationic and hydrophobic amino acids that can target and permeate the mitochondrial membrane. Herein, a novel d-argine-phenylalanine-d-argine-phenylalanine-d-argine-phenylalanine-NH2 (rFrFrF) was tagged with a rhodamine-based fluorescent chromophore (TAMRA). This probe (TAMRA-rFrFrF) exhibited advantageous properties for long-term mitochondria tracking as demonstrated by fluorescence microscopy. Cell viability assays and oxygen consumption rates indicate low cytotoxicity and high biocompatibility of the new contrast agent. Colocalization studies suggest that TAMRA-rFrFrF is a promising candidate for continuous mitochondrial tracking for up to 3 days.

Far-red BODIPY-based oxime esters: photo-uncaging and drug delivery.

Far-red BODIPY-based oxime esters for photo-uncaging were designed to release molecules of interest with carboxylic acids. The low power red LED light breaks the N-O oxime ester bond and frees the caged molecules. We studied the mechanism and kinetics of the uncaging procedure using a 1H NMR spectrometer. Moreover, the drug delivery strategy to release valproic acid (VPA) on demand was tested in vitro using this far-red BODIPY photo-uncaging strategy to induce apoptosis in tumor cells.