Lithium metal batteries have been considerably limited by the problems of uncontrolled dendritic lithium formation and the highly reactive nature of lithium with electrolytes. Herein, we have developed functional porous bilayer composite separators by simply blade-coating polyacrylamide-grafted graphene oxide molecular brushes onto commercial polypropylene separators. Our functional porous bilayer composite separators integrate the lithiophilic feature of hairy polyacrylamide chains and fast electrolyte diffusion pathways with the excellent mechanical strength of graphene oxide nanosheets and thus enable molecular-level homogeneous and fast lithium ionic flux on the surfaces of electrodes. As a result, dendrite-free uniform lithium deposition with a high Coulombic efficiency (98%) and ultralong-term reversible lithium plating/stripping (over 2600 h) at a high current density (2 mA cm−2) are achieved for lithium metal anodes. Remarkably, lithium metal anodes with an unprecedented stability of more than 1900 h cycling at an ultrahigh current density of 20 mA cm−2 are demonstrated.
The development of Pt IV prodrugs that are reduced into the therapeutically active Pt II species within the tumor microenvironment has received much research interest. In order to provide spatial and temporal control over the treatment, there is a high demand for the development of compounds that could be selectively activated upon irradiation. Despite recent progress, the majority of Pt IV complexes are excited with ultraviolet or blue light, limiting the use of such compounds to superficial application. To overcome this limitation, herein, the first example of Pt IV prodrug nanoparticles that could be reduced with deeply penetrating ultrasound radiation is reported, enabling the treatment of deep-seated or large tumors. The nanoparticles were found to selectively accumulate inside a mouse colon carcinoma tumor upon intravenous injection and were able to eradicate the tumor upon exposure to ultrasound radiation.
Glaucoma is the leading cause of irreversible blindness
worldwide,
characterized by progressive vision loss due to the selective damage
to retinal ganglion cells (RGCs) and their axons. Oxidative stress
is generally believed as one key factor of RGCs death. Recently, necroptosis
was identified to play a key role in glaucomatous injury. Therefore,
depletion of reactive oxygen species (ROS) and inhibition of necroptosis
in RGCs has become one of treatment strategies for glaucoma. However,
existing drugs without efficient drug enter into the retina and have
controlled release due to a short drug retention. Herein, we designed
a glaucomatous microenvironment-responsive drug carrier polymer, which
is characterized by the presence of thioketal bonds and 1,4-dithiane
unit in the main chain for depleting ROS as well as the pendant cholesterols
for targeting cell membranes. This polymer was adopted to encapsulate
an inhibitor of necroptosis, necrostatin-1, into nanoparticles (designated
as NP1). NP1 with superior biosafety could scavenge ROS in RGCs both in vitro and in vivo of an acute pathological
glaucomatous injury model. Further, NP1 was found to effectively inhibit
the upregulation of the necroptosis pathway, reducing the death of
RGCs. The findings in this study exemplified the use of nanomaterials
as potential strategies to treat glaucoma.
Selective activation of Pt(IV) prodrugs within tumors is particularly attractive because of their low damage to normal tissues. However, current common activation via chemical/photoreduction of Pt(IV) prodrugs into Pt(II) counterparts is limited by undesirable spatial–temporal control over this reduction process and the ineffective tissue penetration depth of undesirable light. Here, a pseudo‐conjugated‐polymer is designed via Stille polymerization, resulting in PSP‐Pt with a Pt(IV) prodrug of oxaliplatin (Oxa(IV)) in the polymer main chain that can be activated by NIR‐II light. PSP‐Pt can co‐assemble with a commercially available lipid polymer, namely mPEG2k‐DSPE, into NPPSP‐Pt. Under 1064 nm light irradiation, NPPSP‐Pt can be photoactivated to accelerate the Pt(IV) reduction to release oxaliplatin, thereby killing the cancer cells by photothermal effect and chemo‐immunotherapy inside a mouse model with CT26 colon cancer. This work reports the application of NIR‐II light for accelerating Pt(IV) reduction for cancer tumor therapy.
Glutathione S‐transferase (GST), which is a key enzyme in the conjugation reaction of glutathione (GSH), is overexpressed in cancer cells, leading to cisplatin deactivation and ultimately drug resistance. In addition, many tumors are immune “cold tumors,” limiting the application of immune checkpoint inhibitors. Herein, a reactive oxygen species (ROS)‐responsive polyphotosensitizer‐based nanoparticle (NP2) with Michael addition acceptors inhibiting GST activity and cisplatin deactivation is designed. Under the 808 nm light irradiation, on the one hand, the Michael addition acceptor in NP2 can react with GST and inhibit its activity, thereby decreasing the GSH conjugation and reducing the GSH‐mediated deactivation of cisplatin and improving its chemotherapeutic effect. On the other hand, NP2+L induces more ROS production in prostate tumor cells, which can further induce type II immunogenic cell death (ICD) and stimulate a stronger antitumor immune response. It is found that NP2 under the 808 nm light irradiation (NP2+L) can increase PD‐L1 expression on the surface of prostate cancer cells. Subsequently, NP2+L combined with PD‐L1 treatment is found to simultaneously enhance the efficacies of chemotherapy and photodynamic immunotherapy in prostate tumors, providing a new paradigm for the clinical multimodal treatment of tumors.
Die Entwicklung von Pt IV -Prodrugs, die in der Mikroumgebung des Tumors zu therapeutisch aktiven Pt II -Spezies reduziert werden, hat großes Forschungsinteresse geweckt. Um eine räumliche und zeitliche Kontrolle über die Behandlung zu ermöglichen, besteht ein großer Bedarf an der Entwicklung von Verbindungen, die bei Bestrahlung selektiv aktiviert werden können. Trotz jüngster Forschungsfortschritte werden die meisten Pt IV -Komplexe mit ultraviolettem oder blauem Licht angeregt, was die Verwendung solcher Verbindungen für oberflächliche Anwendungen einschränkt. Um diese Einschränkung zu überwinden, wird hier über das erste Beispiel von Pt IV -Prodrug Nanopartikeln berichtet, die mit tief eindringender Ultraschallstrahlung reduziert werden können, was die Behandlung von tiefsitzenden oder großen Tumoren ermöglicht. Es wurde festgestellt, dass sich die Nanopartikel nach intravenöser Injektion selektiv in einem Kolonkarzinom-Tumor der Maus anreichern und den Tumor bei Bestrahlung mit Ultraschall zerstören können.
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