Nanorobots mediated drug delivery for brain cancer active targeting and controllable therapeutics.

Brain cancer pose significant life-threats by destructively invading normal brain tissues, causing dysneuria, disability and death, and its therapeutics is limited by underdosage and toxicity lying in conventional drug delivery that relied on passive delivery. The application of nanorobots-based drug delivery systems is an emerging field that holds great potential for brain cancer active targeting and controllable treatment. The ability of nanorobots to encapsulate, transport, and supply therapies directly to the lesion site through blood-brain barriers makes it possible to deliver drugs to hard-to-reach areas.

Genome-wide impact of codon usage bias on translation optimization in Drosophila melanogaster.

Accuracy and efficiency are fundamental to mRNA translation. Codon usage bias is widespread across species. Despite the long-standing association between optimized codon usage and improved translation, our understanding of its evolutionary basis and functional effects remains limited.

GDF-15 is a potential candidate biomarker for an elevated risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy.

Objective: Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine that regulates myocardial injury, cardiac overloading pressure, and inflammation and is related to the risk of cardiovascular diseases and events. The current study aimed to investigate the correlation of GDF-15 levels with clinical features, biochemical indices, and especially the risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy.

Methods: A total of 103 HER2-positive breast cancer patients who underwent neoadjuvant dual anti-HER2 therapy (trastuzumab and pertuzumab plus chemotherapy) were included.

High-Performance Hybrid Phototheranostics for NIR-IIb Fluorescence Imaging and NIR-II-Excitable Photothermal Therapy.

Photothermal therapy operated in the second near-infrared (NIR-II, 1000-1700 nm) window and fluorescence imaging in the NIR-IIb (1500-1700 nm) region have become the most promising techniques in phototheranostics. Their combination enables simultaneous high-resolution optical imaging and deep-penetrating phototherapy, which is essential for high-performance phototheranostics. Herein, carboxyl-functionalized small organic photothermal molecules (Se-TC) and multi-layered NIR-IIb emissive rare-earth-doped nanoparticles (NaYF:Yb,Er,Ce@NaYF:Yb,Nd@NaYF, RENP) were rationally designed and successfully synthesized.

Artificial intelligence-aided optical imaging for cancer theranostics.

The use of artificial intelligence (AI) to assist biomedical imaging have demonstrated its high accuracy and high efficiency in medical decision-making for individualized cancer medicine. In particular, optical imaging methods are able to visualize both the structural and functional information of tumors tissues with high contrast, low cost, and noninvasive property. However, no systematic work has been performed to inspect the recent advances on AI-aided optical imaging for cancer theranostics.

Deep Learning Aided Neuroimaging and Brain Regulation.

Currently, deep learning aided medical imaging is becoming the hot spot of AI frontier application and the future development trend of precision neuroscience. This review aimed to render comprehensive and informative insights into the recent progress of deep learning and its applications in medical imaging for brain monitoring and regulation. The article starts by providing an overview of the current methods for brain imaging, highlighting their limitations and introducing the potential benefits of using deep learning techniques to overcome these limitations.

Analysis of the molecular composition of humic substances and their effects on physiological metabolism in maize based on untargeted metabolomics.

Introduction: Humic substances (HSs), components of plant biostimulants, are known to influence plant physiological processes, nutrient uptake and plant growth, thereby increasing crop yield. However, few studies have focused on the impact of HS on overall plant metabolism, and there is still debate over the connection between HS' structural characteristics and their stimulatory actions.

Methods: In this study, two different HSs (AHA, Aojia humic acid and SHA, Shandong humic acid) screened in a previous experiment were chosen for foliar spraying, and plant samples were collected on the tenth day after spraying (62 days after germination) to investigate the effects of different HSs on photosynthesis, dry matter accumulation, carbon and nitrogen metabolism and overall metabolism in maize leaf.

Analysis of metabolic differences in maize in different growth stages under nitrogen stress based on UPLC-QTOF-MS.

Introduction: Maize has a high demand for nitrogen during the growth period. The study of metabolic changes in maize can provide a theoretical basis for rational nitrogen nutrition regulation.

Methods: In order to investigate the changes of different metabolites and their metabolic pathways in maize leaves under nitrogen stress, we used ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) for metabolomic analysis of maize leaves under different nitrogen treatments at three critical growth stages (V4, V12 and R1) in a pot experiment under natural conditions.

Breast Cancer Cell Membrane Camouflaged Lipid Nanoparticles for Tumor-Targeted NIR-II Phototheranostics.

Photoacoustic imaging and photothermal therapy that employ organic dye in the second near-infrared window (NIR-II) became an attractive theranostical strategy for eliminating solid tumors, in which IR1048 was previously reported to be a good candidate. However, the further biomedical application of IR1048 was blocked by its poor water-solubility and lack of tumor-targeting. To solve this problem, liposome camouflaged with 4T1 cell membrane fragments was employed to encapsulate IR1048 (thereafter called MLI), and its application for photoacoustic and thermo-imaging and photothermal therapy were explored in vitro and in vivo.

Efficacy and safety of neoadjuvant pyrotinib plus docetaxel/liposomal doxorubicin/cyclophosphamide for HER2-positive breast cancer.

Objective: Pyrotinib is a novel EGFR/HER2 dual tyrosine kinase inhibitor developed in China, while its role in neoadjuvant therapy of HER2-positive (HER2) breast cancer lacks evidence. The current study aimed to explore the efficacy and safety of neoadjuvant pyrotinib plus docetaxel/liposomal doxorubicin/cyclophosphamide (TAC) for HER2 breast cancer.

Methods: A total of 27 HER2 breast cancer patients received neoadjuvant pyrotinib plus TAC for 6 cycles, then surgery was performed.

Phototheranostic Metal-Phenolic Networks with Antiexosomal PD-L1 Enhanced Ferroptosis for Synergistic Immunotherapy.

Tumor-derived exosome can suppress dendritic cells (DCs) and T cells functions. Excessive secretion of exosomal programmed death-ligand 1 (PD-L1) results in therapeutic resistance to PD-1/PD-L1 immunotherapy and clinical failure. Restored T cells by antiexosomal PD-L1 tactic can intensify ferroptosis of tumor cells and vice versa.

Second near-infrared photoactivatable biocompatible polymer nanoparticles for effective in vitro and in vivo cancer theranostics.

Photoacoustic imaging (PAI)-guided photothermal therapy (PTT) has drawn considerable attention due to the deeper tissue penetration and higher maximum permissible exposure. However, current phototheranostic agents are greatly restricted by weak absorption in the second near-infrared (NIR-II, 1000-1700 nm) window, long-term toxicity, and poor photostability. In this report, novel organic NIR-II conjugated polymer nanoparticles (CPNs) based on narrow bandgap donor-acceptor BDT-TBZ polymers were developed for effective cancer PAI and PTT.

Supramolecular Tropism Driven Aggregation of Nanoparticles In Situ for Tumor-Specific Bioimaging and Photothermal Therapy.

Inorganic nanomedicine has attracted increasing attentions in biomedical sciences due to their excellent biocompatibility and tunable, versatile functionality. However, the relatively poor accumulation and retention of these nanomedicines in targeted tissues have often hindered their clinical translation. Herein, highly efficient, targeted delivery, and in situ aggregation of ferrocene (Fc)-capped Au nanoparticles (NPs) are reported to cucurbit[7]uril (CB[7])-capped Fe O NPs (as an artificial target) that are magnetically deposited into the tumor, driven by strong, multipoint CB[7]-Fc host-guest interactions (here defined as "supramolecular tropism" for the first time), leading to high tumor accumulation and retention of these NPs.

Temperature-Feedback Nanoplatform for NIR-II Penta-Modal Imaging-Guided Synergistic Photothermal Therapy and CAR-NK Immunotherapy of Lung Cancer.

In this study, to visually acquire all-round structural and functional information of lung cancer while performing synergistic photothermal therapy (PTT) and tumor-targeting immunotherapy, a theranostic nanoplatform that introduced upconversion nanoparticles (UCNPs) and IR-1048 dye into the lipid-aptamer nanostructrure (UCILA) is constructed. Interestingly, the IR-1048 dye grafted into the lipid bilayer can serve as the theranostic agent for photoacoustic imaging, optical coherence tomography angiography, photothermal imaging, and PTT in the second near infrared (NIR-II) window. In addition, loaded in the inner part of UCILA, UCNPs possess the superior luminescence property and high X-ray attenuation coefficient, which can act as contrast agents for computed tomography (CT) and thermo-sensitive up-conversion luminescence (UCL) imaging, enabling real-time tracking of metabolic activity of tumor and temperature-feedback PTT.

A hypoxia responsive nanoassembly for tumor specific oxygenation and enhanced sonodynamic therapy.

The hypoxic tumor microenvironment (TME) and non-specific distribution of sonosensitizers are two major obstacles that limit practical applications of sonodynamic therapy (SDT) in combating tumors. Here we report a hypoxia-responsive nanovesicle (hMVs) as delivery vehicles of a sonosensitizer to enhance the efficacy of SDT via specific payload release and local oxygenation in the tumor. The nanovesicles are composed of densely packed manganese ferrite nanoparticles (MFNs) embedded in hypoxia-responsive amphiphilic polymer membranes.

Inhibiting tumor oxygen metabolism and simultaneously generating oxygen by intelligent upconversion nanotherapeutics for enhanced photodynamic therapy.

Hypoxia is one of the hallmarks of solid tumor, which heavily restricts the clinical cancer therapy treatments, especially for the oxygen (O) -dependent photodynamic therapy (PDT). Herein, an intelligent multi-layer nanostructure was developed for decreasing the O-consumption and elevating the O-supply simultaneously. The cell respiration inhibitor -atovaquone (ATO) molecules were reserved in the middle mesoporous silicon layer, and thus were intelligently released at the tumor site after the degradation of gatekeeper of MnO layer, which effectively inhibit tumor respiration metabolism to elevate oxygen content.

ROS-Responsive Berberine Polymeric Micelles Effectively Suppressed the Inflammation of Rheumatoid Arthritis by Targeting Mitochondria.

Rheumatoid arthritis (RA) is an autoimmune disease, which attacks human joint system and causes lifelong inflammatory condition. To date, no cure is available for RA and even the ratio of achieving remission is very low. Hence, to enhance the efficacy of RA treatment, it is essential to develop novel approaches specifically targeting pathological tissues.

pH-sensitive loaded retinal/indocyanine green micelles as an "all-in-one" theranostic agent for multi-modal imaging in vivo guided cellular senescence-photothermal synergistic therapy.

In this study, pH-sensitive loaded retinal/indocyanine green (ICG) micelles were developed to realize novel approaches for cellular senescence-photothermal synergistic therapy to treat cancer. The micelles could enable effective multi-modal imaging in vivo guided therapy and show anticancer activity in vitro and in vivo with satisfactory biosafety.

Dual-Modal In Vivo Fluorescence/Photoacoustic Microscopy Imaging of Inflammation Induced by GFP-Expressing Bacteria.

In this study, dual-modal fluorescence and photoacoustic microscopy was performed for noninvasive and functional in vivo imaging of inflammation induced by green fluorescent protein (GFP) transfected bacteria in mice ear. Our imaging results demonstrated that the multimodal imaging technique is able to monitor the tissue immunovascular responses to infections with molecular specificity. Our study also indicated that the combination of photoacoustic and fluorescence microscopy imaging can simultaneously track the biochemical changes including the bacterial distribution and morphological change of blood vessels in the biological tissues with high resolution and enhanced sensitivity.

Multispectral photoacoustic imaging of cancer with broadband CuS nanoparticles covering both near-infrared I and II biological windows.

In this study, CuS nanoparticles with optical absorption covering both near-infrared I (NIR-I) and NIR-II biological windows were prepared and served as the contrast agents for multispectral photoacoustic imaging. The physiological parameters including concentrations of deoxyhemoglobin and oxyhemoglobin as well as the water content in the tumor location were quantified based on the multispectral photoacoustic reconstruction method. More importantly, the concentration of CuS nanoparticles/drugs accumulated in the tumor was also recovered after intravenously injection, which are essential for image-guided cancer theranostics.

Dimeric camptothecin-loaded RGD-modified targeted cationic polypeptide-based micelles with high drug loading capacity and redox-responsive drug release capability.

Camptothecin (CPT) is a broad spectrum anticancer drug, but its application is limited due to the poor water solubility, lactone ring instability, and low drug loading potential. In this study, biocompatible cationic polypeptide-based micelles were developed to deliver dimeric CPT (DCPT) with the aim of overcoming the above-mentioned obstacles and achieving favorable therapeutic effects. Cationic polypeptide poly-lysine-block-poly-leucine (PLys-b-PLeu) was fabricated via the ring-opening polymerization of N-ε-carbobenzoxy-l-lysine (ε-Lys(Z)) and l-leucine (Leu) and further grafted with polyethylene glycol (PEG) and an arginine-glycine-aspartic acid (RGD) peptide.

Design, synthesis, anticancer activity and docking studies of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives as mTOR inhibitors.

A series of 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives (7a-q, 10a-q) were designed, synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR, MS and HRMS spectrum.All the compounds were evaluated for the inhibitory activity against mTOR kinase at 10 μM level. Five selected compounds (7b, 7e, 7h, 10b and 10e) were further evaluated for the inhibitory activity against PI3Ka at 10 μM level, and the IC50 values against mTOR kinase and two cancer cell lines.

Mechanism of the hairpin folding transformation of thymine-cytosine-rich oligonucleotides induced by Hg(II) and Ag(I) ions.

The metal-induced folding of thymine-cytosine-rich oligonucleotides into hairpin-like structures was characterised by isothermal titration calorimetry, secondary structure analysis, equilibrium titrations, and fluorescence study. We find that designed thymine-cytosine-rich oligonucleotides can specifically bind with Hg(II) or Ag(I) ions to generate metal-mediated base pairs in a hairpin-like structure from a random coil structure. Isothermal titration calorimetry experiments were performed to reveal the detail of the whole binding process.