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. In this review, we demonstrated how AI can guide optical imaging methods to improve the accuracy on tumor detection, automated analysis and prediction of its histopathological section, its monitoring during treatment, and its prognosis by using computer vision, deep learning and natural language processing. By contrast, the optical imaging techniques involved mainly consisted of various tomography and microscopy imaging methods such as optical endoscopy imaging, optical coherence tomography, photoacoustic imaging, diffuse optical tomography, optical microscopy imaging, Raman imaging, and fluorescent imaging. Meanwhile, existing problems, possible challenges and future prospects for AI-aided optical imaging protocol for cancer theranostics were also discussed. It is expected that the present work can open a new avenue for precision oncology by using AI and optical imaging tools.

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. Then, we further delve into the details of deep learning, explaining the basic concepts and providing examples of how it can be used in medical imaging. One of the key strengths is its thorough discussion of the different types of deep learning models that can be used in medical imaging including convolutional neural networks (CNNs), recurrent neural networks (RNNs), and generative adversarial network (GAN) assisted magnetic resonance imaging (MRI), positron emission tomography (PET)/computed tomography (CT), electroencephalography (EEG)/magnetoencephalography (MEG), optical imaging, and other imaging modalities. Overall, our review on deep learning aided medical imaging for brain monitoring and regulation provides a referrable glance for the intersection of deep learning aided neuroimaging and brain regulation.

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. Diminishing exosomal suppression and establishing a nexus of antiexosomal PD-L1 and ferroptosis may rescue the discouraging antitumor immunity. Here, we engineered phototheranostic metal-phenolic networks (PFG MPNs) by an assembly of semiconductor polymers encapsulating ferroptosis inducer (Fe3+) and exosome inhibitor (GW4869). The PFG MPNs elicited superior near-infrared II fluorescence/photoacoustic imaging tracking performance for a precise photothermal therapy (PTT). PTT-augmented immunogenic cell death relieved exosomal silencing on DC maturation. GW4869 mediated PD-L1 based exosomal inhibition revitalized T cells and enhanced the ferroptosis. This novel synergy of PTT with antiexosomal PD-L1 enhanced ferroptosis evoked potent antitumor immunity in B16F10 tumors and immunological memory against metastatic tumors in lymph nodes.

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. Furthermore, under the complementary guidance of penta-modal imaging and an accurate monitoring of in situ temperature change during PTT, UCILA exhibits its excellent capability for ablating the lung tumor with minimal side effects. Meanwhile, synergistic CAR-NK immunotherapy is carried out specifically to eradicate any possible residual tumor cells after PTT. Therefore, the UCILA nanoplatform is demonstrated as a multifunctional theranostic agent for both penta-modal imaging and temperature-feedback PTT while conducting targeting immunotherapy of lung cancer.

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 Fe3 O4 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. The in vitro and in vivo studies demonstrate the precisely controlled, specific accumulation, and retention of Au NPs in the tumor cells and tissue via supramolecular tropism and in situ aggregation, which afford locally enhanced CT imaging of cancer and enable tumor-specific photothermal therapy attributed to the plasmonic coupling effects between adjacent Au NPs within the supramolecular aggregations. This work provides a novel concept of supramolecular tropism, which may drive targeted delivery and enable specific accumulation, retention, and activation of nanomedicine for improved bioimaging and therapy of cancer.

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. Consequently, the developed method paves a new avenue for improving the understanding of the pathology mechanism of inflammation.

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. Twelve of the target compounds exhibited moderate antitumor activities. The most promising compound 7e showed strong antitumor activities against mTOR kinase, H460 and PC-3 cell lines with IC50 values of 0.80 ± 0.15 µM, 7.43 ± 1.45 µM and 11.90 ± 0.94 µM, which were 1.28 to 1.71-fold more active than BMCL-200908069-1 (1.37 ± 0.07 µM, 9.52 ± 0.29 µM, 16.27 ± 0.54 µM), respectively. Structure-activity relationships (SARs) and docking studies indicated that the thiopyrano[4,3-d]pyrimidine scaffolds exerted little effect on antitumor activities of target compounds. Substitutions of aryl group at C-4 position had a significant impact on the antitumor activities, and 4-OH substitution produced the best potency.

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. Serum GDF-15 levels before neoadjuvant treatment were detected by enzyme-linked immunosorbent assay. Cardiotoxicity was evaluated during neoadjuvant therapy by referring to a decline of ≥10 percentage points in the left ventricular ejection fraction from baseline to an absolute level less than 50%. Results: GDF-15 exhibited a skewed distribution, with a median level of 714 (range: 207-1805) pg/mL. GDF-15 was positively correlated with age (p = 0.037), diabetes (p = 0.036), and the N-terminal pro-brain natriuretic peptide level (p = 0.013) and positively correlated with the total cholesterol level (p = 0.086) and troponin T level (p = 0.082), but these correlations were not statistically significant. A total of 6.8% of patients experienced cardiotoxicity during neoadjuvant therapy. By comparison, the GDF-15 level was greater in patients who experienced cardiotoxicity than in those who did not (p = 0.008). A subsequent receiver operating characteristic curve revealed that GDF-15 predicted cardiotoxicity risk, with an area under the curve of 0.803 (95% CI: 0.664-0.939). After multivariate adjustment, GDF-15 independently predicted a greater risk of cardiotoxicity (p = 0.020). Conclusion: GDF-15 is a candidate biomarker for increased risk of cardiotoxicity in breast cancer patients receiving neoadjuvant dual anti-HER2 therapy.

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. The thermodynamic result exhibits two possible pathways of significant change upon the addition of Hg(II) ions. Furthermore, this transformation can be enhanced by the presence of Ag(I) ions. The fluorescence decreases through fluorescence resonance energy transfer (FRET) between the fluorophore and quencher confirms the process of formation of the hairpin-like structure. The analysis of optical titration data demonstrates that the saturated binding stoichiometries are 12:1 and 4:1 for Hg(II) and Ag(I) ions, respectively. Our result provides a promising strategy for the investigation of the mechanism of structural transformation of oligonucleotides influenced by metal-mediated base pairs, which may eventually lead to progress in constructing a metal-triggered DNA origami system and metal-containing DNA nanotechnology.

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. The clinical and pathological responses, and adverse events were evaluated. RESULTS: Complete response rate, objective response rate, and disease control rate were 0.0%, 44.4% and 100.0% after 2 treatment cycles; 0.0%, 37.0%, and 100.0% after 4 treatment cycles; 37.0%, 37.0%, and 96.3% after 6 treatment cycles; as well as 37.0%, 44.4%, and 100.0% based on the best clinical response. Regarding pathological response, there were 1 (2.7%), 3 (11.1%), 8 (29.6%), 5 (18.5%), and 10 (37.0%) patients realizing Miller-Payne grade (G) 1, G2, G3, G4, and G5, respectively; besides, 10 (37.0%) patients achieved total pathological complete response (pCR), 10 (37.0%) patients realized pCR in breast, and 23 (85.2%) patients achieved pCR in lymph node. Additionally, adverse events included diarrhea (81.5%), dental ulcer (7.4%), and hand-foot syndrome (3.7%); meanwhile, grade 3-4 adverse event consisted of only diarrhea (11.1%). CONCLUSION: Neoadjuvant pyrotinib plus TAC treatment is efficient and safe in HER2+ breast cancer patients, while further validation is needed.

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. Results and discussion: The results showed that nitrogen stress significantly affected sugar metabolism and nitrogen metabolism, and affected carbon and nitrogen balance, and the effects of stress on maize leaves metabolism increased with the growth process. Metabolic pathways such as the TCA cycle and starch and sucrose metabolism were mainly affected at the seeding stage (V4). The stress response to nitrogen deficiency also showed significant upregulation of flavonoids such as luteolin and astragalin during the booting stage (V12) and anthesis-silking stage (R1). During R1 stage, the synthesis of tryptophan and phenylalanine and the degradation of lysine were significantly affected. Compared with nitrogen stress, the metabolic synthesis of key amino acids and jasmonic acid were intensified and the TCA cycle was promoted under nitrogen sufficiency conditions. This study initially revealed that the response mechanism of maize to nitrogen stress at the metabolic level.

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 (NaYF4:Yb,Er,Ce@NaYF4:Yb,Nd@NaYF4, RENP) were rationally designed and successfully synthesized. Then, high-performance hybrid phototheranostic nanoagents (Se-TC@RENP@F) were easily constructed through the coordination between Se-TC and RENP and followed by subsequent F127 encapsulation. The carboxyl groups of Se-TC can offer strong binding affinity towards rare-earth-doped nanoparticles, which help improving the stability of Se-TC@RENP@F. The multilayered structure of RENP largely enhance the NIR-IIb emission under 808 nm excitation. The obtained Se-TC@RENP@F exhibited high 1064 nm absorption (extinction coefficient: 24.7 L g-1 cm-1), large photothermal conversion efficiency (PCE, 36.9%), good NIR-IIb emission (peak: 1545 nm), as well as great photostability. Upon 1064 nm laser irradiation, high hyperthermia can be achieved to kill tumor cells efficiently. In addition, based on the excellent NIR-IIb emission of Se-TC@RENP@F, in vivo angiography and tumor detection can be realized. This work provides a distinguished paradigm for NIR-IIb-imaging-guided NIR-II photothermal therapy and establishes an artful strategy for high-performance phototheranostics.

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. Results and discussion: The results showed different molecular compositions for AHA and SHA and a total of 510 small molecules with significant differences were screened using an ESI-OPLC-MS techno. AHA and SHA exerted different effects on maize growth, with the AHA inducing more effective stimulation than the SHA doing. Untargeted metabolomic analysis revealed that the phospholipid components of maize leaves treated by SHA generally increased significantly than that in the AHA and control treatments. Additionally, both HS-treated maize leaves exhibited different levels of accumulation of trans-zeatin, but SHA treatment significantly decreased the accumulation of zeatin riboside. Compared to CK treatment, AHA treatment resulted in the reorganization of four metabolic pathways: starch and sucrose metabolism, TCA cycle, stilbenes, diarylheptanes, and curcumin biosynthesis, and ABC transport, SHA treatment modified starch and sucrose metabolism and unsaturated fatty acid biosynthesis. These results demonstrate that HSs exert their function through a multifaceted mechanism of action, partially connected to their hormone-like activity but also involving hormoneindependent signaling pathways.

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. The results showed that MLI exhibited spherical morphology around 92.55 ± 5.41 nm coated by monolayer adventitial fragments, and uniformly dispersed in PBS with high loading efficiency and encapsulation efficiency to IR1048. In addition, both free IR1048 and MLI presented strong absorption in NIR-II, and upon 1064 nm laser irradiation the MLI showed awesome photothermal performance that could rapidly elevate the temperature to 50.9 °C in 6 min. Simultaneously, phantom assay proved that MLI could dramatically enhance the photoacoustic amplitudes by a linear concentration-dependent way. Moreover, either flow cytometry or confocal analysis evidenced that MLI was the most uptaked by 4T1 cells among other melanoma B16 cells and Hek293 cells and coexist of IR1048 and 1064 nm laser irradiation were indispensable for the photothermal cytotoxicity of MLI that specifically killed 96.16% of 4T1 cells far outweigh the B16 cells while hardly toxic to the Hek293 normal cells. Furthermore, PA imaging figured out that 4 h post tail-vein injection of MLI was the best time to give 1064 nm irradiation to conduct the photothermal therapy when the average tumor-accumulation of MLI achieved the highest. In the NIR-II photothermal therapy, MLI could significantly inhibit the tumor growth and almost ablated the tumors with slight body weight variation and the highest average life span over the therapy episode and caused no damage to the normal organs. Hence, MLI could pave the way for further biomedical applications of IR-1048 by homologous tumor-targeting and dual-modal imaging directed NIR-II accurate photothermal therapy with high efficacy and fine biosafety.

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. Characterization data confirmed the high photothermal conversion efficiency, good photostability, excellent PAI performance, and superior biocompatibility of as-obtained CPNs. In addition, in vitro and in vivo tests demonstrated the efficient PTT effect of CPNs in ablating cancer cells and inhibiting tumor growth under 1064 nm laser irradiation. More importantly, the CPNs exhibited rapid clearance capability through the biliary pathway and negligible systematic toxicity. Thus, this work provides a novel organic theranostic nanoplatform for NIR-II PAI-guided PTT, which advances the future clinical translation of biocompatible and metabolizable conjugated nanomaterials in cancer diagnosis and therapy.

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. With δ-aminolevulinic acid (ALA) loaded in the hollow cavities, the hMVs could rapidly dissociate into discrete nanoparticles in the hypoxic TME to release the payload and induce the generation of reactive oxygen species (ROS) under ultrasound (US) radiation. Meanwhile, the released MFNs could catalytically generate O2 to overcome the hypoxic TME and thus enhance the efficacy of SDT. After treatment, the dissociated MFNs could be readily excreted from the body via renal clearance to reduce long term toxicity. In vitro and in vivo experiments displayed effective tumor inhibition via hMVs-mediated SDT, indicating the great potential of this unique nanoplatform in effective SDT by generating sufficient ROS in deep-seated hypoxic tumors that are not readily accessible by conventional photodynamic therapy.

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. In this study, we discovered that RA synovial fibroblasts exhibited higher reactive oxygen species (ROS) and mitochondrial superoxide level, which were adopted to develop ROS-responsive nano-medicines in inflammatory microenvironment for enhanced RA treatment. A selenocystamine-based polymer was synthesized as a ROS-responsive carrier nanoplatform, and berberine serves as a tool drug. By assembling, ROS-responsive berberine polymeric micelles were fabricated, which remarkably increased the uptake of berberine in RA fibroblast and improved in vitro and in vivo efficacy ten times higher. Mechanistically, the anti-RA effect of micelles was blocked by the co-treatment of AMPK inhibitor or palmitic acid, indicating that the mechanism of micelles was carried out through targeting mitochondrial, suppressing lipogenesis and finally inhibiting cellular proliferation. Taken together, our ROS-responsive nano-medicines represent an effective way of preferentially releasing prodrug at the inflammatory microenvironment and improving RA therapeutic efficacy.

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 (O2) -dependent photodynamic therapy (PDT). Herein, an intelligent multi-layer nanostructure was developed for decreasing the O2-consumption and elevating the O2-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 MnO2 layer, which effectively inhibit tumor respiration metabolism to elevate oxygen content. Meanwhile, the degradation of MnO2 layer can generate O2, further boosting oxygen content. Moreover, the inner upconversion nanostructures as the near infrared (NIR) light-transducers enable to activate photosensitizers for deep-tissue PDT. Systematic experiments demonstrate that this suppressing O2-consumption and O2-generation strategy improved oxygen supply to boost the singlet oxygen generation to eradicate cancer cells under NIR light excitation. Better still, superior trimodality imaging capabilities (computed tomography (CT), NIR-II window fluorescence, and tumor microenvironment-responsive T1-weighted magnetic resonance (MR) imaging) of the nanoplatform were evaluated. Our findings offer a promising aproach to conquer the serious hypoxia problem in cancer therapy by turning down the O2 metabolism aveneue and simultaneously generating O2.

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. In addition, phantom and in vivo experimental tests were performed to inspect and compare the imaging depth and signal-to-noise ratio (SNR) between the two NIR biological windows. Interestingly, we discovered that a higher SNR was obtained in the NIR-II window than that in the NIR-I window. Meanwhile, the multispectral imaging results also demonstrated that the imaging contrast and penetration depth in the NIR-II window were also significantly improved as compared to those from the NIR-I window.

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.