Ultrathin BSA-Stabilized Black Phosphorous Nanoreactor Boosts Mild-Temperature Photothermal Therapy Through Modulation of Cellular Self-Defense Fate.

Mild-temperature photothermal therapy (mild-PTT, 42-45 °C) offers a higher level of biosafety. However, its therapeutic effects are compromised by the heat shock response (HSR), a cellular self-defense mechanism, which triggers the overexpression of heat shock proteins (HSPs) with the capacity of repairing the damaged tumor cells. Herein, this work fabricates a novel nanoreactor by incorporating up-conversion nanoparticles (UCNPs), chlorin e6 (Ce6), and glucose oxidase (GOx) onto the ultrathin black phosphorus nanosheet (BPNS) (denoted as GOx-BUC). This nanoreactor amplifies mild-PTT effects under irradiation with an 808 nm laser, modulating HSPs-mediated cellular self-defense fate. On one hand, upon irradiation with a 980 nm laser, UCNPs can transfer energy to excite Ce6, leading to the generation of ROS burst, which achieves indiscriminate damage to HSPs activity in deeper tumor tissues. On the other hand, GOx can consume glucose, thereby depleting the ATP energy supply and further suppressing HSPs expression. Consequently, GOx-BUC exhibits excellent anti-tumor efficacy under mild temperature in a human colorectal cancer mouse model, resulting in complete tumor inhibition with negligible side effects. This black phosphorous nanoreactor, featuring dual-track HSPs destruction functionality, introduces novel perspectives for enhancing mild-PTT effectiveness while maintaining high biosafety.

Regenerating Chemotherapeutics through Copper-Based Nanomedicine: Disrupting Protein Homeostasis for Enhanced Tumor Therapy.

The bis-(diethyldithiocarbamate)-copper (CuET), the disulfiram (DSF)-Cu complex, has exhibited noteworthy anti-tumor property. However, its efficacy is compromised due to the inadequate oxidative conditions and the limitation of bioavailable copper. Because CuET can inactivate valosin-containing protein (VCP), a bioinformatic pan-cancer analysis of VCP is first conducted in this study to identify CuET as a promising anticancer drug for diverse cancer types. Then, based on the drug action mechanism, a nanocomposite of CuET and copper oxide (CuO) is designed and fabricated utilizing bovine serum albumin (BSA) as the template (denoted as CuET-CuO@BSA, CCB). CCB manifests peroxidase (POD)-mimicking activity to oxidize the tumor endogenous H2O2 to generate reactive oxygen species (ROS), enhancing the chemotherapy effect of CuET. Furthermore, the cupric ions released after enzymatic reaction can regenerate CuET, which markedly perturbs intracellular protein homeostasis and induces apoptosis of tumor cells. Meanwhile, CCB triggers cuproptosis by inducing the aggregation of lipoylated proteins. The multifaceted action of CCB effectively inhibits tumor progression. Therefore, this study presents an innovative CuET therapeutic strategy that creates an oxidative microenvironment in situ and simultaneously self-supply copper source for CuET regeneration through the combination of CuO nanozyme with CuET, which holds promise for application of CuET for effective tumor therapy.

Black Phosphorus/MnO2 Nanocomposite Disrupting Bacterial Thermotolerance for Efficient Mild-Temperature Photothermal Therapy.

The emergence of multi-drug resistant (MDR) pathogens is a major public health concern, posing a substantial global economic burden. Photothermal therapy (PTT) at mild temperature presents a promising alternative to traditional antibiotics due to its biological safety and ability to circumvent drug resistance. However, the efficacy of mild PTT is limited by bacterial thermotolerance. Herein, a nanocomposite, BP@Mn-NC, comprising black phosphorus nanosheets and a manganese-based nanozyme (Mn-NZ) is developed, which possesses both photothermal and catalytic properties. Mn-NZ imparts glucose oxidase- and peroxidase-like properties to BP@Mn-NC, generating reactive oxygen species (ROS) that induce lipid peroxidation and malondialdehyde accumulation across the bacterial cell membrane. This process disrupts unprotected respiratory chain complexes exposed on the bacterial cell membrane, leading to a reduction in the intracellular adenosine triphosphate (ATP) content. Consequently, mild PTT mediated by BP@Mn-NC effectively eliminates MDR infections by specifically impairing bacterial thermotolerance because of the dependence of bacterial heat shock proteins (HSPs) on ATP molecules for their proper functioning. This study paves the way for the development of a novel photothermal strategy to eradicate MDR pathogens, which targets bacterial HSPs through ROS-mediated inhibition of bacterial respiratory chain activity.

A Novel Teaching-Learning-Based Optimization with Error Correction and Cauchy Distribution for Path Planning of Unmanned Air Vehicle.

Teaching-learning-based optimization (TLBO) algorithm is a novel heuristic method which simulates the teaching-learning phenomenon of a classroom. However, in the later period of evolution of the TLBO algorithm, the lower exploitation ability and the smaller scope of solutions led to the poor results. To address this issue, this paper proposes a novel version of TLBO that is augmented with error correction strategy and Cauchy distribution (ECTLBO) in which Cauchy distribution is utilized to expand the searching space and error correction to avoid detours to achieve more accurate solutions. The experimental results verify that the ECTLBO algorithm has overall better performance than various versions of TLBO and is very competitive with respect to other nine original intelligence optimization algorithms. Finally, the ECTLBO algorithm is also applied to path planning of unmanned aerial vehicle (UAV), and the promising results show the applicability of the ECTLBO algorithm for problem-solving.