Mitochondria are
crucial in the process of oxidative metabolism
and apoptosis. Their morphology is greatly associated with the development
of certain diseases. For specific and long-term imaging of mitochondrial
morphology, we synthesized a new mitochondria-targeted near-infrared
(NIR) fluorescent probe (TPE–Xan–In) by incorporating
TPE with a NIR merocyanine skeleton (Xan–In). TPE–Xan–In
displayed both absorption (660 nm) and emission peaks (743 nm) in
the NIR region. Moreover, it showed aggregation-induced emission properties
at neutral pH and specifically illuminated mitochondria with good
biocompatibility, superior photostability, and high tolerance to mitochondrial
membrane potential changes. With a pH-responsive unit, hydroxyl xanthene
(Xan), the probe exhibited a pH-sensitive fluorescence emission in
the range of pH 4.0–7.0, which indicated its potential in long-term
tracking of pH and morphology changes of mitochondria in the biomedical
research studies.
Extensive
attention has been recently focused on designing signal
adjustable biosensors. However, there are limited approaches available
in this field. In this work, to visually track lysosomes with high
contrast, we used the i-motif structure as a pH-responsive unit and
proposed a novel strategy to regulate the fluorescence resonance energy
transfer (FRET) response of the pH sensor. By simply splitting the
i-motif into two parts and modulating the split parameters, we can
tune the pH transition midpoint (pHt) from 5.71 to 6.81
and the signal-to-noise ratio (S/N) from 1.94 to 18.11. To facilitate
the lysosome tracking, we combined the i-motif split design with tetrahedral
DNA (Td). The obtained pH nanosensor (pH-Td) displays appropriate
pHt (6.12) to trace lysosomes with high S/N (10.3). Benefited
from the improved stability, the superior cell uptake and lysosomal
location of pH-Td, the visualization of the distribution of lysosomes,
the lysosome–mitochondria interaction, and the pH changes of
lysosomes in response to different stimuli were successfully achieved
in NIH 3T3 cells. We believe that the design concept of controlling
the split sequence distance will provide a novel insight into the
design of i-motif-based nanosensors and even inspire the construction
of smart DNA nanodevices for sensing, disease diagnosis, and controllable
drug delivery.
Reliable
and accurate glucose detection in biological samples is
of great importance in clinical diagnosis and medical research. Chemical
probes are advantageous in simple operation and flexible design, especially
for the development of fluorescent probes. Anthracene-based diboronic
acid (P-DBA) has shown potential in glucose probing because of its
high sensitivity. However, poor solubility limits its applications
in aqueous media. In this work, we systemically modify P-DBA by introducing
fluoro (F-), chloro (Cl-), methoxyl (MeO-), or cyano (CN-) substituents.
Among these probes, the cyano-substituted probe (CN-DBA) displays
the highest glucose-binding constant (6489.5 M–1, 33% MeOH). More importantly, it shows good water solubility in
the aqueous solution (0.5% MeOH), with ultrasensitive recognition
with glucose (LOD = 1.51 μM) and robust sensing from pH 6.0
to 9.0. Based on these features, the CN-DBA is finally applied to
detect glucose in cell lysates and plasma, with satisfactory recovery
and precision. These results demonstrate that CN-DBA could serve as
an accurate, sensitive fluorescent probe for glucose assays in biological
samples.
With the rapid development of nanotechnology, researchers have designed a variety of intelligent nanodelivery systems to enhance tumor targeting of anticancer drugs. However, increased tumor accumulation does not indicate deeper penetration in the tumor tissue, without which the tumor cells in the core area cannot be sufficiently killed. Herein, we develop a size-controllable nanoparticle system for deep-penetrating cancer therapy, which will be programmably disassembled with the decrease of the pH from the normal tissue to the tumor microenvironment and to the intracellular area. The integrated nanoparticle is composed of a gold nanoparticle (GNP, ∼30 nm) and a tetrahedral DNA nanostructure (TDN, ∼25 nm) loaded with doxorubicin (DOX). Initially, the nanoparticles maintain a larger size (∼100 nm) to accumulate in the tumor through the enhanced permeability and retention effect. At a pH of about 6.5 at the tumor microenvironment, with the linkage of DNA sequences converting into a triplex structure, the TDNs detach from the GNP and penetrate deeply into the tumor interstitium and then are internalized into the cells. Finally, in acidic lysosomes with pH 5.0, the TDNs release DOX by forming an i-motif structure. This nanosmart delivery system thus shows effective deep penetration into the tumor core with good antitumor efficacy and satisfactory biocompatibility and provides new insights into the development of intelligent nanosystems for anti-cancer treatment.
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