Fluorescent
organic nanoparticles (FONs) are emerging as an attractive
alternative to the well-established fluorescent inorganic nanoparticles
or small organic dyes. Their proper design allows one to obtain biocompatible
probes with superior brightness and high photostability, although
usually affected by low colloidal stability. Herein, we present a
type of FONs with outstanding photophysical and physicochemical properties
in-line with the stringent requirements for biomedical applications.
These FONs are based on quatsome (QS) nanovesicles containing a pair
of fluorescent carbocyanine molecules that give rise to Förster
resonance energy transfer (FRET). Structural homogeneity, high brightness,
photostability, and high FRET efficiency make these FONs a promising
class of optical bioprobes. Loaded QSs have been used for in vitro
bioimaging, demonstrating the nanovesicle membrane integrity after cell internalization, and the possibility
to monitor the intracellular vesicle fate. Taken together, the proposed
QSs loaded with a FRET pair constitute a promising platform for bioimaging
and theranostics.
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-arginephenylalanine-D-argine-phenylalanine-D-argine-phenylalanine-NH 2 (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.
Chemoresistance is one of the major challenges for cancer treatment, more recently ascribed to defective mitochondrial outer membrane permeabilization (MOMP), significantly diminishing chemotherapeutic agent‐induced apoptosis. A boron‐dipyrromethene (BODIPY) chromophore‐based triarylsulfonium photoacid generator (BD‐PAG) was used to target mitochondria with the aim to regulate mitochondrial pH and further depolarize the mitochondrial membrane. Cell viability assays demonstrated the relative biocompatibility of BD‐PAG in the dark while live cell imaging suggested high accumulation in mitochondria. Specific assays indicated that BD‐PAG is capable of regulating mitochondrial pH with significant effects on mitochondrial membrane depolarization. Therapeutic tests using chlorambucil in combination with BD‐PAG revealed a new strategy in chemoresistance suppression.
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