Strong oxygen dependence,
poor tumor targeting, and limited treatment
depth have been considered as the “Achilles’ heels”
facing the clinical usage of photodynamic therapy (PDT). Different
from common approaches, here, we propose an innovative tactic by using
photon-initiated dyad cationic superoxide radical (O2
–•) generator (ENBOS) featuring
“0 + 1 > 1” amplification effect to simultaneously
overcome
these drawbacks. In particular, by taking advantage of the Förster
resonance energy transfer theory, the energy donor successfully endows ENBOS with significantly enhanced NIR absorbance and photon
utility, which in turn lead to ENBOS more easily activated
and generating more O2
–• in deep
tissues, that thus dramatically intensifies the type I PDT against
hypoxic deep tumors. Moreover, benefiting from the dyad cationic feature, ENBOS achieves superior “structure-inherent targeting”
abilities with the signal-to-background ratio as high as 25.2 at 48
h post intravenous injection, offering opportunities for accurate
imaging-guided tumor treatment. Meanwhile, the intratumoral accumulation
and retention performance are also markedly improved (>120 h).
On
the basis of these unique merits, ENBOS selectively inhibits
the deep-seated hypoxic tumor proliferation at a low light-dose irradiation.
Therefore, this delicate design may open new horizons and cause a
paradigm change for PDT in future cancer therapy.
It remains a considerable
challenge to realize complete tumor suppression
and avoid tumor regrowth by rational design of photosensitizers (PSs)
to improve their photon utilization. In this Article, we provide a
molecular design (Icy-NBF) based on the oxygen-content-regulated
deactivation process of excited states. In the presence of overexpressed
nitroreductase in hypoxic cancer cells, Icy-NBF is reduced
and converted into a molecule with the same skeleton (Icy-NH
2
), in which the deactivation of the PS under
808 nm light irradiation proceeds via a different pathway: the excited
states deactivation pathway of Icy-NBF involves radiative
transition and energy transfer between Icy-NBF and O2; as for Icy-NH
2
, the
deactivation pathway is attributed to non-radiative relaxation. By
varying the O2 concentration in tumor cells, the therapeutic
mechanism of Icy-NBF under 808 nm light irradiation can
be switched between photodynamic and photothermal therapies, which
maximizes the advantages of phototherapies with no tumor regrowth.
Our study provides help in designing of smart PSs with improvement
of photon utilization for efficient tumor photoablation.
A palladium phosphide electrocatalyst supported on carbon black (PdP2@CB) shows efficient water splitting in both alkaline and neutral electrolytes. Significantly lower overpotentials are required for PdP2@CB (27.5 mV in 0.5 m H2SO4; 35.4 mV in 1 m KOH; 84.6 mV in 1 m PBS) to achieve a HER electrocatalytic current density of 10 mA cm−2 compared to commercial Pt/CB (30.1 mV in 0.5 m H2SO4; 46.6 mV in 1 m KOH; 122.7 mV in 1 m PBS). Moreover, no loss in HER activity is detectable after 5000 potential sweeps. Only 270 mV and 277 mV overpotentials are required to reach a current density of 10 mA cm−2 for PdP2@CB to catalyze OER in 1 m KOH and 1 m PBS electrolytes, which is better OER activity than the benchmark IrO2 electrocatalyst (301 mV and 313 mV to drive a current density of 10 mA cm−2). 1.59 V and 1.72 V are needed for PdP2@CB to achieve stable water splitting catalytic current density of 10 mA cm−2 in 1 m PBS and 50 mA cm−2 in 1 m KOH for 10 h, respectively.
Structure-inherent
targeting (SIT) agents are of particular importance
for clinical precision medicine; however, there still exists a great
lack of SIT phototheranostics for simultaneous cancer diagnosis and
targeted photodynamic therapy (PDT). Herein, for the first time, we
propose a “one-for-all” strategy by using the Förster
resonance energy transfer (FRET) mechanism to construct such omnipotent
SIT phototheranostics. Of note, this novel tactic can not only endow
conventional sensitizers with highly effective native tumor-targeting
potency but also simultaneously improve their photosensitization activities,
resulting in dramatically boosted therapeutic index. After intravenous
injection of the prepared SIT theranostic, the neoplastic sites are
distinctly “lighted up” and distinguished from neighboring
tissues, showing a near-infrared signal-to-background ratio value
as high as 12.5. More importantly, benefiting from the FRET effect,
markedly amplified light-harvesting ability and 1O2 production are demonstrated. Better still, other favorable
features are also simultaneously achieved, including specific mitochondria
anchoring, augmented cellular uptake (>13-fold), as well as ideal
biocompatibility, all of which allow orders-of-magnitude promotion
in anticancer efficiency both in vitro and in vivo. We believe this
one-for-all SIT platform will provide a new idea for future cancer
precision therapy.
The proline-rich Akt substrate of 40 kDa (PRAS40) is a substrate of Akt and a component of the mammalian target of rapamycin complex 1 (mTORC1). Locating at the crossroad of the PI3K/Akt pathway and the mTOR pathway, PRAS40 is phosphorylated by growth factors or other stimuli, and regulates the activation of these signaling pathways in turn. PRAS40 plays an important role in metabolic disorders and multiple cancers, and the phosphorylation of PRAS40 is often associated with the tumor progression of melanoma, prostate cancer, etc. PRAS40 promotes tumorigenesis by deregulating cellular proliferation, apoptosis, senescence, metastasis, etc. Herein, we provide an overview on current understandings of PRAS40 signaling in the tumor formation and progression, which suggests that PRAS40 or phospho-PRAS40 could become a novel biomarker and therapeutic target in tumor.
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