Dendritic Plasmonic CuPt Alloys for Closed-Loop Multimode Cancer Therapy with Remarkably Enhanced Efficacy.

The outcome of laser-triggered plasmons-induced phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is significantly limited by the hypoxic tumor microenvironment and the upregulation of heat shock proteins (HSPs) in response to heat stress. Mitochondria, the biological battery of cells, can serve as an important breakthrough to overcome these obstacles. Herein, dendritic triangular pyramidal plasmonic CuPt alloys loaded with heat-sensitive NO donor N, N'-di-sec-butyl-N, N'-dinitroso-1,4-phenylenediamine (BNN) is developed. Under 808 nm laser irradiation, plasmonic CuPt can generate superoxide anion free radicals (·O2 - ) and heat simultaneously. The heat generated can then trigger the release of NO gas, which not only enables gas therapy but also damages the mitochondrial respiratory chain. Impaired mitochondrial respiration leads to reduced oxygen consumption and insufficient intracellular ATP supply, which effectively alleviates tumor hypoxia and undermines the synthesis of HSPs, in turn boosting plasmonic CuPt-based PDT and mild PTT. Additionally, the generated NO and ·O2 - can react to form more cytotoxic peroxynitrite (ONOO- ). This work describes a plasmonic CuPt@BNN (CPB) triggered closed-loop NO gas, free radicals, and mild photothermal therapy strategy that is highly effective at reciprocally promoting antitumor outcomes.

A Multifunctional Nanovaccine based on L-Arginine-Loaded Black Mesoporous Titania: Ultrasound-Triggered Synergistic Cancer Sonodynamic Therapy/Gas Therapy/Immunotherapy with Remarkably Enhanced Efficacy.

In order to achieve better antitumor therapeutic efficacy and inhibit tumor metastasis, a multifunctional nanovaccine based on L-arginine (LA)-loaded black mesoporous titania (BMT) is fabricated. In this system, LA is utilized as the exogenous NO supplementation for gas therapy, and BMT is served as acoustic sensitizer for sonodynamic therapy. The ultrasound (US) as the exogenous stimulus can simultaneously trigger BMT and LA to produce singlet oxygen (1 O2 ) and NO gas at tumor sites, respectively. Interestingly, 1 O2 from US-excited BMT can promote the oxidation of LA to produce more NO. The high concentration of 1 O2 and NO in cancer cell can cause intracellular strong oxidative stress level and DNA double-strand breaks to induce cancer cell apoptosis ultimately. The US-triggered BMT@LA "nanovaccine" combining with immune checkpoint inhibitor PD-L1 antibody (αPD-L1) can induce strong antitumor immune response thus effectively killing primary tumors and further inhibiting metastatic tumors. Hence, BMT@LA-based "nanovaccine" combining with αPD-L1 checkpoint blockade treatment can realize synergetic sonodynamic/gas/immunotherapy with enhanced antitumor therapeutic effects.

NIR-Triggered Multi-Mode Antitumor Therapy Based on Bi2 Se3 /Au Heterostructure with Enhanced Efficacy.

Of all the reaction oxygen species (ROS) therapeutic strategies, NIR light-induced photocatalytic therapy (PCT) based on semiconductor nanomaterials has attracted increasing attention. However, the photocatalysts suffer from rapid recombination of electron-hole pairs due to the narrow band gaps, which are greatly restricted in PCT application. Herein, Bi2 Se3 /Au heterostructured photocatalysts are fabricated to solve the problems by introducing Au nanoparticles (NPs) in situ on the surface of the hollow mesoporous structured Bi2 Se3 . Owing to the lower work function of Au NPs, the photo-induced electrons are easier to transfer and assemble on their surfaces, resulting in the increased separation of the electron-hole pairs with efficient ROS generation. Besides, Bi2 Se3 /Au heterostructures also enhance the photothermal efficiency due to the effective orbital overlaps with accelerated electron migrations according to density functional theory calculations. Moreover, the PLGA-PEG and the doxorubicin (DOX) are introduced for photothermal-triggered drug release in the system. The Bi2 Se3 /Au heterostructures also displays excellent infrared thermal (IRT) and computed tomography (CT) dual-modal imaging property for promising cancer diagnosis. Collectively, Bi2 Se3 /Au@PLGA-PEG-DOX exhibits prominent tumor inhibition effect based on synchronous PTT, PCT and chemotherapy triggered by NIR light for efficient antitumor treatment.

NADPH Oxidase-Like Nanozyme for High-Efficiency Tumor Therapy Through Increasing Glutathione Consumption and Blocking Glutathione Regeneration.

To counteract the high level of reactive oxygen species (ROS) caused by rapid growth, tumor cells resist oxidative stress by accelerating the production and regeneration of intracellular glutathione (GSH). Numerous studies focus on the consumption of GSH, but the regeneration of GSH will enhance the reduction level of tumor cells to resist oxidative stress. Therefore, inhibiting the regeneration of GSH; while, consuming GSH is of great significance for breaking the redox balance of tumor cells. Herein, a simple termed MnOx-coated Au (AMO) nanoflower, as a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) nanoenzyme, is reported for efficient tumor therapy. Au nanoparticles exhibit the capability to catalyze the oxidation of NADPH, hindering GSH regeneration; while, concurrently functioning as a photothermal agent. During the process of eliminating intracellular GSH, MnOx releases Mn2+ that subsequently engages in Fenton-like reactions, ultimately facilitating the implementation of chemodynamic therapy (CDT). Overall, this NOX enzyme-based nanoplatform enhances ROS generation and disrupts the state of reduction equilibrium, inducing apoptosis and ferroptosis by blocking GSH regeneration and increasing GSH consumption, thereby achieving collaborative treatments involving photothermal therapy (PTT), CDT, and catalytic therapy. This research contributes to NADPH and GSH targeted tumor therapy and showcases the potential of nanozymes.

Strategies for Designing Antithermal-Quenching Red Phosphors.

Nowadays, red phosphor plays a key role in improving the lighting quality and color rendering index of phosphor-converted white light emitting diodes (w-LEDs). However, the development of thermally stable and highly efficient red phosphor is still a pivotal challenge. Herein, a new strategy to design antithermal-quenching red emission in Eu3+, Mn4+-codoped phosphors is proposed. The photoluminescence intensity of Mg3Y2(1- y )Ge3O12:yEu3+, Mn4+ (0 ≤ y ≤ 1) phosphors continuously enhances with rising temperature from 298 to 523 K based on Eu3+ → Mn4+ energy transfer. For Mg3Eu2Ge3O12:Mn4+ sample, the integrated intensity at 523 K remarkably reaches 120% of that at 298 K. Interestingly, through codoping Eu3+ and Mn4+ in Mg3Y2Ge3O12, the photoluminescence color is controllably tuned from orangish-red (610 nm) to deep-red (660 nm) light by changing Eu3+ concentration. The fabricated w-LEDs exhibit superior warm white light with low corrected color temperature (CCT = 4848 K) and high color rendering index (R a = 96.2), indicating the promising red component for w-LED applications. Based on the abnormal increase in antistokes peaks of Mn4+ with temperatures, Mg3Eu2Ge3O12:Mn4+ phosphor also presents a potential application in optical thermometry sensors. This work initiates a new insight to construct thermally stable and spectra-tunable red phosphors for various optical applications.