Full-course NIR-II imaging-navigated fractionated photodynamic therapy of bladder tumours with X-ray-activated nanotransducers.

The poor 5-year survival rate for bladder cancers is associated with the lack of efficient diagnostic and treatment techniques. Despite cystoscopy-assisted photomedicine and external radiation being promising modalities to supplement or replace surgery, they remain invasive or fail to provide real-time navigation. Here, we report non-invasive fractionated photodynamic therapy of bladder cancer with full-course real-time near-infrared-II imaging based on engineered X-ray-activated nanotransducers that contain lanthanide-doped nanoscintillators with concurrent emissions in visible and the second near-infrared regions and conjugated photosensitizers. Following intravesical instillation in mice with carcinogen-induced autochthonous bladder tumours, tumour-homing peptide-labelled nanotransducers realize enhanced tumour regression, robust recurrence inhibition, improved survival rates, and restored immune homeostasis under X-ray irradiation with accompanied near-infrared-II imaging. On-demand fractionated photodynamic therapy with customized doses is further achieved based on quantifiable near-infrared-II imaging signal-to-background ratios. Our study presents a promising non-invasive strategy to confront the current bladder cancer dilemma from diagnosis to treatment and prognosis.

Consistency of CSCO AI with Multidisciplinary Clinical Decision-Making Teams in Breast Cancer: A Retrospective Study.

Background: The Chinese Society of Clinical Oncology Artificial Intelligence System (CSCO AI) serves as a clinical decision support system developed utilizing Chinese breast cancer data. Our study delved into the congruence between breast cancer treatment recommendations provided by CSCO AI and their practical application in clinical settings. Methods: A retrospective analysis encompassed 537 breast cancer patients treated at the Second Affiliated Hospital of Anhui Medical University between January 2017 and December 2022. Proficient senior oncology researchers manually input patient data into the CSCO AI system. "Consistent" and "Inconsistent" treatment categories were defined by aligning our treatment protocols with the classification system in the CSCO AI recommendations. Cases that initially showed inconsistency underwent a second evaluation by the Multi-Disciplinary Treatment (MDT) team at the hospital. Concordance was achieved when MDTs' treatment suggestions were in the 'Consistent' categories. Results: An impressive 80.4% concurrence was observed between actual treatment protocols and CSCO AI recommendations across all breast cancer patients. Notably, the alignment was markedly higher for stage I (85.02%) and stage III (88.46%) patients in contrast to stage II patients (76.06%, P=0.023). Moreover, there was a significant concordance between invasive ductal carcinoma and lobular carcinoma (88.46%). Interestingly, triple-negative breast cancer (TNBC) exhibited a high concordance rate (87.50%) compared to other molecular subtypes. When contrasting MDT-recommended treatments with CSCO AI decisions, an overall 92.4% agreement was established. Furthermore, a logistic multivariate analysis highlighted the statistical significance of age, menstrual status, tumor type, molecular subtype, tumor size, and TNM stage in influencing consistency. Conclusion: In the realm of breast cancer treatment, the alignment between recommendations offered by CSCO AI and those from MDT is predominant. CSCO AI can be a useful tool for breast cancer treatment decisions.

Dual-signal detection of tannic acid in red wines based on the peroxidase activity of carbon dots.

Herein, a novel type of phosphorus and iron-doped carbon dot (P,Fe-CD) with outstanding peroxidase activity and excellent fluorescence performance was hydrothermally synthesized to colorimetrically and fluorimetrically detect tannic acid (TA). In the presence of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2, the P,Fe-CDs could oxidize colorless TMB to a blue oxidation product (oxTMB) resulting in an increased value of absorbance. Simultaneously, the fluorescence intensity of P,Fe-CDs at 430 nm could be quenched owing to the fluorescence resonance energy transfer (FRET) between P,Fe-CDs and the generated oxTMB. Meanwhile, after adding the TA to the system containing TMB, H2O2 and P,Fe-CDs, the value of absorbance could be decreased and the fluorescence could be recovered because of the reduction reaction between TA and oxTMB. Therefore, fluorescence intensity and value of absorbance could be applied to quantitatively detect TA with good linearities between the concentration of TA and the fluorescence intensity/value of absorbance (0.997 and 0.997 for the colorimetric signal and fluorimetric one, respectively) and low limits of detection (0.093 µmol L-1 and 0.053 µmol L-1 for the colorimetry and the fluorimetry, respectively), which was successfully applied to the detection of TA in red wines. Moreover, we applied a smartphone-assisted method to the point-of-care detection of TA with accurate results, providing a new technique for TA detection and food quality monitoring.

Exploring CCL11 in breast cancer: unraveling its anticancer potential and immune modulatory effects involving the Akt-S6 signaling.

BACKGROUND: CCL11, a chemokine known for recruiting immune cells to the tumor microenvironment (TME), has an unclear role in the context of its expression, patient prognosis, and the presence of tumor-infiltrating immune cells (TILs) in breast cancer. METHODS: The expression of CCL11 in invasive breast cancer (BRCA) was analyzed using TCGA database. Survival curve and Cox regression analysis determined the potential of CCL11 as an independent prognostic indicator. GSEA performed functional analysis on genes related to CCL11. CIBERSORT algorithm quantified the infiltration level of immune cells with varying CCL11 expression. Lastly, the correlation between CCL11 expression and anticancer drug sensitivity was examined. Immunohistochemistry (IHC) and qRT-PCR confirmed CCL11 expression in clinical tissue samples. The anti-tumor efficacy of CCL11 was investigated using CCK-8, plate formation, transwell assay, and Western blot. RESULTS: CCL11 expression was elevated in BRCA tumor tissues compared to adjacent normal tissues. Recurrence-free survival (RFS) was longer in patients with high expression of CCL11. Enrichment and co-expression analyses revealed CCL11's association with numerous immune-related signaling pathways and genes. Validation studies confirmed high CCL11 expression in breast cancer tissues. In vitro experiments substantiated CCL11's anticancer effects in BRCA. CONCLUSION: CCL11 expression correlates with immune cell infiltration in breast cancer, indicating its potential as a prognostic biomarker for BRCA.

FUS-Mediated CircFGFR1 Accelerates the Development of Papillary Thyroid Carcinoma by Stabilizing FGFR1 Protein.

Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer and its incidence is rising globally. The molecular mechanisms of PTC progression remain unclear, hindering the development of effective treatments. This study focuses on hsa_circ_0008016 (circFGFR1), a circular RNA significantly up-regulated in PTC cells. Silencing circFGFR1 inhibited PTC cell proliferation and increased cell apoptosis, suggesting its role in PTC progression. The RNA-binding protein FUS was identified as a promoter of circFGFR1 formation. While circFGFR1 does not influence FGFR1 mRNA translation, it inhibits ubiquitination and degradation of FGFR1 protein, prolonging its half-life. CircFGFR1 also interacts with protein CBL, inhibiting CBL-mediated ubiquitination of FGFR1 proteins. Rescue assays confirmed circFGFR1 promotes PTC cell growth through mediating FGFR1. This study highlights the potential of circFGFR1 as a therapeutic target, offering insights into PTC's molecular mechanisms, and paving the way for novel treatment strategies.

CD1C is associated with breast cancer prognosis and immune infiltrates.

BACKGROUND: The tumor microenvironment (TME) in breast cancer plays a vital role in occurrence, development, and therapeutic responses. However, immune and stroma constituents in the TME are major obstacles to understanding and treating breast cancer. We evaluated the significance of TME-related genes in breast cancer. METHODS: Invasive breast cancer (BRCA) samples were retrieved from the TCGA and GEO databases. Stroma and immune scores of samples as well as the proportion of tumor infiltrating immune cells (TICs) were calculated using the ESTIMATE and CIBERSORT algorithms. TME-related differentially expressed genes (DEGs) were analyzed by a protein interaction (PPI) network and univariate Cox regression to determine CD1C as a hub gene. Subsequently, the prognostic value of CD1C, its response to immunotherapy, and its mechanism in the TME were further studied. RESULTS: In BRCA, DEGs were determined to identify CD1C as a hub gene. The expression level of CD1C in BRCA patients was verified based on the TCGA database, polymerase chain reaction (PCR) results, and western blot analysis. Immunohistochemical staining (IHC) results revealed a correlation between prognosis, clinical features, and CD1C expression in BRCA. Enrichment analysis of GSEA and GSVA showed that CD1C participates in immune-associated signaling pathways. CIBERSORT showed that CD1C levels were associated with tumor immune infiltrating cells (TILs), such as different kinds of T cells. Gene co-expression analysis showed that CD1C and the majority of immune-associated genes were co-expressed in BRCA. In renal cell carcinoma, patients with a high expression of CD1C had a better immunotherapy effect. CONCLUSION: CD1C is an important part of the TME and participates in immune activity regulation in breast tumors. CD1C is expected to become a prognostic marker and a new treatment target for breast cancer.

Silent region barcode particle arrays for ultrasensitive multiplexed SERS detection.

Suspension arrays are a critical components of next generation multiplexed detection technologies. Current fluorescence suspension arrays are limited by a multiplexed coding ceiling and difficulties with ultrasensitive detection. Raman mode is a promising substitute, but the complex spectral peak distributions and extremely weak intrinsic signal intensity severely diminish Raman signal performance in suspension arrays. To address these limitations, we constructed a Raman suspension array system using plasmonic microbeads as barcode substrates and Au nanoflowers as reporter carriers. The well-designed shell morphology and plasmonic microbead composition enabled significant surface enhancement Raman scattering (SERS) such that we were able to adjust silent region Raman-coding intensity levels. Due to synergistic SERS effects from the plasmonic shell and the multi-branched Au nanoflower nanostructure, the reporting signal was greatly improved, enabling ultrasensitive detection of 5-plexed lung cancer markers. Detection in patient serum samples demonstrated good consistency with the standard electrochemiluminescence method. Thus, this silent region SERS barcode-based suspension array is a developmental advance for modern multiplexed biodetection, potentially providing a powerful early disease screening and diagnosis tool.

Recent Progress and Trends in X-ray-Induced Photodynamic Therapy with Low Radiation Doses.

The prominence of photodynamic therapy (PDT) in treating superficial skin cancer inspires innovative solutions for its congenitally deficient shadow penetration of the visible-light excitation. X-ray-induced photodynamic therapy (X-PDT) has been proven to be a successful technique in reforming the conventional PDT for deep-seated tumors by creatively utilizing penetrating X-rays as external excitation sources and has witnessed rapid developments over the past several years. Beyond the proof-of-concept demonstration, recent advances in X-PDT have exhibited a trend of minimizing X-ray radiation doses to quite low values. As such, scintillating materials used to bridge X-rays and photosensitizers play a significant role, as do diverse well-designed irradiation modes and smart strategies for improving the tumor microenvironment. Here in this review, we provide a comprehensive summary of recent achievements in X-PDT and highlight trending efforts using low doses of X-ray radiation. We first describe the concept of X-PDT and its relationships with radiodynamic therapy and radiotherapy and then dissect the mechanism of X-ray absorption and conversion by scintillating materials, reactive oxygen species evaluation for X-PDT, and radiation side effects and clinical concerns on X-ray radiation. Finally, we discuss a detailed overview of recent progress regarding low-dose X-PDT and present perspectives on possible clinical translation. It is expected that the pursuit of low-dose X-PDT will facilitate significant breakthroughs, both fundamentally and clinically, for effective deep-seated cancer treatment in the near future.

Bioinformatics and Experimental Analysis of the Prognostic and Predictive Value of the CHPF Gene on Breast Cancer.

Background: Recent studies in the United States have shown that breast cancer accounts for 30% of all new cancer diagnoses in women and has become the leading cause of cancer deaths in women worldwide. Chondroitin Polymerizing Factor (CHPF), is an enzyme involved in chondroitin sulfate (CS) elongation and a novel key molecule in the poor prognosis of many cancers. However, its role in the development and progression of breast cancer remains unclear. Methods: The transcript expression of CHPF in the Cancer Genome Atlas-Breast Cancer (TCGA-BRCA), Gene Expression Omnibus (GEO) database was analyzed separately using the limma package of R software, and the relationship between CHPF transcriptional expression and CHPF DNA methylation was investigated in TCGA-BRCA. Kaplan-Meier curves were plotted using the Survival package to further assess the prognostic impact of CHPF DNA methylation/expression. The association between CHPF transcript expression/DNA methylation and cancer immune infiltration and immune markers was investigated using the TIMER and TISIDB databases. We also performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with the clusterProfiler package. Western blotting and RT-PCR were used to verify the protein level and mRNA level of CHPF in breast tissue and cell lines, respectively. Small interfering plasmids and lentiviral plasmids were constructed for transient and stable transfection of breast cancer cell lines MCF-7 and SUM1315, respectively, followed by proliferation-related functional assays, such as CCK8, EDU, clone formation assays; migration and invasion-related functional assays, such as wound healing assay and transwell assays. We also conducted a preliminary study of the mechanism. Results: We observed that CHPF was significantly upregulated in breast cancer tissues and correlated with poor prognosis. CHPF gene transcriptional expression and methylation are associated with immune infiltration immune markers. CHPF promotes proliferation, migration, invasion of the breast cancer cell lines MCF-7 and SUM1315, and is significantly enriched in pathways associated with the ECM-receptor interaction and PI3K-AKT pathway. Conclusion: CHPF transcriptional expression and DNA methylation correlate with immune infiltration and immune markers. Upregulation of CHPF in breast cancer promotes malignant behavior of cancer cells and is associated with poorer survival in breast cancer, possibly through ECM-receptor interactions and the PI3K-AKT pathway.

One-Pot Access to Ethylene-Bridged BODIPY Dimers and Trimers through Single-Electron Transfer Chemistry.

A Cu(I)-promoted oxidative dimerization of BODIPY dyes was developed to give a series of α,α- ethylene-bridged BODIPY dimers and trimers for the first time. This methodology does not need harsh conditions but relies on the singlet-electron-transfer process between alkylated BODIPYs and Cu(I) salt to generate BODIPY-based radical species, which undergo a selective radical homocoupling reaction. Moreover, these resultant dimers and trimers showed high attenuation coefficients, small line widths of the absorption and emission, and intense fluorescence.

Magnetite Fe3O4 Nanoparticles Enhance Mild Microwave Ablation of Tumor by Activating the IRE1-ASK1-JNK Pathway and Inducing Endoplasmic Reticulum Stress.

PURPOSE: With the development of nanomedicine, microwave ablation enhanced by multifunctional nanoplatforms has been widely studied for synergistic cancer therapy. Though scientists have got a lot of significant achievements in this field, the detailed molecular mechanisms and potential targets of microwave ablation enhanced by multifunctional nanoplatforms still need further exploration. In this study, we found that a kind of magnetite Fe3O4 nanoparticles (Fe3O4 NPs) could induce severe endoplasmic reticulum stress and activate cancer apoptosis under the irradiation of mild microwave. METHODS: In this study, plenty of studies including cell immunofluorescence, mitochondrial membrane potential, electron microscopy, atomic force microscopy and microwave ablation in vivo were conducted to explore the molecular mechanisms and potential targets of microwave ablation enhanced by the Fe3O4 NPs. RESULTS: The IRE1-ASK1-JNK pathway was strongly activated in A375 cells treated with both Fe3O4 NPs and mild microwave. The endoplasmic reticulum of the A375 cells was significantly dilated and exhibited ballooning degeneration. By investigating the mitochondrial membrane potential (ΔΨm), we found that the mitochondria of cancer cells had been significantly damaged under microwave treatment coupled with Fe3O4 NPs. In addition, melanoma of B16F10-bearing mice had also been effectively inhibited after being treated with Fe3O4 NPs and microwave. CONCLUSION: In this study, we found that a kind of magnetite Fe3O4 nanoparticles could induce severe ER stress and activate cancer apoptosis under mild microwave irradiation. Apparent apoptosis had been observed in the A375 cells under a scanning electron microscope and transmission electron microscope. Moreover, melanoma had also been inhibited effectively in vivo. As a result, the endoplasmic reticulum stress is a promising target with clinical potential in nanomedicine and cancer therapy.

Long non-coding RNA SNHG8 enhances triple-negative breast cancer cell proliferation and migration by regulating the miR-335-5p/PYGO2 axis.

BACKGROUND: Growing evidence has demonstrated that long non-coding RNAs (lncRNAs) can function as modulators in the development of triple-negative breast cancer (TNBC). However, the function of lncRNA small nucleolar RNA host gene 8 (SNHG8) in TNBC remains unclear. Therefore, our study aimed at investigating the role of SNHG8 in the proliferation and migration of TNBC cells. METHODS: SNHG8 expression was evaluated using RT-qPCR assay. Cell proliferation and migration were assessed by EdU, colony formation and Transwell assays. The levels of proteins related to EMT process were examined by western blot assay. The interaction among SNHG8, miR-335-5p and pygopus family PHD finger 2 (PYGO2) was detected by RIP assay, RNA pull down assay and luciferase reporter assay. RESULTS: SNHG8 expression was significantly up-regulated in TNBC cells. SNHG8 silencing obviously inhibited TNBC cell proliferation, migration and EMT process. Moreover, SNHG8 acted as a sponge to sequester miR-335-5p in TNBC cells. Besides, PYGO2 was proven as a target gene of miR-335-5p, and SNHG8 promoted TNBC cell proliferation, migration and EMT process through regulating miR-335-5p and PYGO2. CONCLUSIONS: Totally, our study indicated that SNHG8 promoted TNBC cell proliferation and migration by regulating the miR-335-5p/PYGO2 axis.

Antiangiogenesis Combined with Inhibition of the Hypoxia Pathway Facilitates Low-Dose, X-ray-Induced Photodynamic Therapy.

X-ray-induced photodynamic therapy (XPDT) is overwhelmingly superior in treating deep-seated cancers. However, limitations remain, owing to a combination of the poor scintillation performance of the nanoscintillator, low energy transfer efficiency of the therapeutic nanoplatform, and hypoxic environment presented in the tumor tissue. Collectively, these reduce the curative effect of XPDT. Here, we report a highly efficient, low-dose XPDT realized by systematic optimization from scintillation efficiency, nanoplatform structure, to therapeutic approach. We developed a biocompatible, codoped CaF2 nanoscintillator that emitted sufficiently green radioluminescence that was bright enough to be seen by the naked eye. Using dendrimers as a framework, we built a nanoplatform featuring a dual-core-satellite architecture, which enabled both procedurally and spatially separate dual-loading of therapeutic agents. This strategy allowed for the fabrication of a combined XPDT and antiangiogenic therapy, resulting in a therapeutic system capable of simultaneous tumor attacks. After exposure to ultralow dose radiation, XPDT resulted in marked tumor reduction while the antiangiogenic drug effectively blocked tumor vascularization exacerbated by XPDT-mediated hypoxia, rendering a pronounced synergy effect. This system also showed high biosafety, as the agents adopted had been used clinically and both Ca and F elements were widespread in the human body. Taken together, the findings presented here provided a reference for the construction of complex, multiloading architecture in coordination with structural complexity and functional diversification. This work provided a safer and more robust application of the combined XPDT and antiangiogenesis in future clinical treatment settings.

A green fabrication method of poly (lactic acid) perforated membrane via tuned crystallization and gas diffusion process.

Poly (lactic acid) (PLA) perforated membrane is typically obtained through the solvent-volatilization-induced or non-solvent-induced phase separation (NIPS) method. However, the residual organic solvents would unavoidably limit the application of PLA perforated membrane in biomedical and high-end water purification fields. Herein, an innovative solution-free method was proposed for preparing the PLA perforated membrane via a simple and environmentally friendly way. We have successfully fabricated the PLA perforated membrane using a physical foaming technique with CO2 as the blowing agent. By tuning the primary film thickness, saturation pressure, and foaming temperature, PLA perforated membrane's cell morphology could be accordingly adjusted. The PLA perforated membrane with a highly-ordered straight pore channel and high open cell content (OCC) approximately 72% was obtained under a mild condition. The formation mechanism of the PLA perforated membrane was discussed via the interaction of crystallization behavior and gas diffusion process. This green and solvent-free PLA perforated membrane possesses great potential for use in areas like the tissue engineering and high-end water purification.

Pnictogen Semimetal (Sb, Bi)-Based Nanomaterials for Cancer Imaging and Therapy: A Materials Perspective.

Innovative multifunctional nanomaterials have attracted tremendous interest in current research by facilitating simultaneous cancer imaging and therapy. Among them, antimony (Sb)- and bismuth (Bi)-based nanoparticles are important species with multifunction to boost cancer theranostic efficacy. Despite the rapid development, the extensive previous work treated Sb- and Bi-based nanoparticles as mutually independent species, and therefore a thorough understanding of their relationship in cancer theranostics was lacking. We propose here that the identical chemical nature of Sb and Bi, being semimetals, provides their derived nanoparticles with inherent multifunction for near-infrared laser-driven and/or X-ray-based cancer imaging and therapy as well as some other imparted functions. An overview of recent progress on Sb- and Bi-based nanoparticles for cancer theranostics is provided to highlight the relationship between chemical nature and multifunction. The understanding of Sb- and Bi-based nanoparticles in this way might shed light on the further design of smart multifunctional nanoparticles for cancer theranostics.

Tetramodal Imaging and Synergistic Cancer Radio-Chemotherapy Enabled by Multiple Component-Encapsulated Zeolitic Imidazolate Frameworks.

The abundant species of functional nanomaterials have attracted tremendous interests as components to construct multifunctional composites for cancer theranostics. However, their distinct chemical properties substantially require a specific strategy to integrate them in harmony. Here, we report the preparation of a distinctive multifunctional composite by encapsulating small-sized semiconducting copper bismuth sulfide (CBS) nanoparticles and rare-earth down-conversion (DC) nanoparticles in larger-sized zeolitic imidazolate framework-8 (ZIF8) nanoparticles, followed by loading an anticancer drug, doxorubicin (DOX). Such composites can be used for tetramodal imaging, including traditional computed tomography and magnetic resonance imaging and, recently, for photoacoustic imaging and fluorescence imaging. With a pH-responsive release of the encapsulated components, synergistic radio-chemotherapy with a high (87.6%) tumor inhibition efficiency is achieved at moderate doses of the CBS&DC-ZIF8@DOX composite with X-ray irradiation. This promising strategy highlights the extending capacity of zeolitic imidazolate frameworks to encapsulate multiple distinct components for enhanced cancer imaging and therapy.

Highly sensitive fluorescence-linked immunosorbent assay based on aggregation-induced emission luminogens incorporated nanobeads.

Aggregation-induced emission luminogens (AIEgens) have attracted considerable interest for application towards the development of various biosensors due to their unique optical properties. However, the major challenge associated with generating a suitable fluorescent signal for constructing an AIEgens-based immunoassay platform, is the complex surface modification and additional chemical reaction required to activate the AIE process. This work reports a novel AIEgens nanobeads-based fluorescence-linked immunosorbent assay (FLISA) platform wherein the fluorescent labels are hexaphenylsilole (HPS) nanobeads, which were synthesized through Shirasu porous glass (SPG) membrane emulsification method and could provide a strong, direct fluorescent signal without any pretreatment. Moreover, the particle-based signal amplification effect affords this platform significantly improved detection sensitivity for carcinoembryonic antigen (CEA) quantitation. Compared to FLISA which uses R-phycoerythrin (PE) or commercial green QDs nanobeads as fluorescent labels, this AIEgens nanobeads-based FLISA platform exhibits detection sensitivity improved up to 45-fold and 12-fold, respectively. Clinical validation experiments applying this AIEgens nanobeads-based FLISA immunoassay platform to analyze human serum samples produce results consistent with those obtained by the clinical gold-standard method, electrochemiluminescence immunoassay (ECLIA). The strong photobleaching resistance and excellent fluorescent stability of the HPS nanobeads negate the need for light shielding, which improves the efficiency and makes the operating conditions more comfortable. Thus, this AIEgens nanobeads-based FLISA platform, with attractive features including direct fluorescent signal generation and significant signal amplification, creates a new, versatile route for the application of AIEgens in biosensors and clinical diagnosis.

Recent Advances in Developing K-Ras Plasma Membrane Localization Inhibitors.

The Ras proteins play an important role in cell growth, differentiation, proliferation and survival by regulating diverse signaling pathways. Oncogenic mutant K-Ras is the most frequently mutated class of Ras superfamily that is highly prevalent in many human cancers. Despite intensive efforts to combat various K-Ras-mutant-driven cancers, no effective K-Ras-specific inhibitors have yet been approved for clinical use to date. Since K-Ras proteins must be associated to the plasma membrane for their function, targeting K-Ras plasma membrane localization represents a logical and potentially tractable therapeutic approach. Here, we summarize the recent advances in the development of K-Ras plasma membrane localization inhibitors including natural product-based inhibitors achieved from high throughput screening, fragment-based drug design, virtual screening, and drug repurposing as well as hit-to-lead optimizations.

W-doped TiO2 nanoparticles with strong absorption in the NIR-II window for photoacoustic/CT dual-modal imaging and synergistic thermoradiotherapy of tumors.

Multifunctional nanomaterials that have integrated diagnostic and therapeutic functions and low toxicity, and can enhance treatment efficacy through combination therapy have drawn tremendous amounts of attention. Herein, a newly developed multifunctional theranostic agent is reported, which is PEGylated W-doped TiO2 (WTO) nanoparticles (NPs) synthesized via a facile organic route, and the results demonstrated strong absorbance of these WTO NPs in the second near-infrared (NIR-II) window due to successful doping with W. These PEGylated WTO NPs can absorb both NIR-II laser and ionizing radiation, rendering them well suited for dual-modal computed tomography/NIR-II photoacoustic imaging and synergistic NIR-II photothermal/radiotherapy of tumors. In addition, the long-term in vivo studies indicated that these PEGylated WTO NPs had no obvious toxicity on mice in vivo, and they can be cleared after a 30-day period. In summary, this multifunctional theranostic agent can absorb both NIR-II laser and ionizing radiation with negligible toxicity and rapid clearance, therefore it has great promise for applications in imaging and therapeutics in biomedicine.

Codoping Enhanced Radioluminescence of Nanoscintillators for X-ray-Activated Synergistic Cancer Therapy and Prognosis Using Metabolomics.

Radio- and photodynamic therapies are the first line of cancer treatments but suffer from poor light penetration and less radiation accumulation in soft tissues with high radiation toxicity. Therefore, a multifunctional nanoplatform with diagnosis-assisted synergistic radio- and photodynamic therapy and tools facilitating early prognosis are urgently needed to fight the war against cancer. Further, integrating cancer therapy with untargeted metabolomic analysis would collectively offer clinical pertinence through facilitating early diagnosis and prognosis. Here, we enriched scintillation of CeF3 nanoparticles (NPs) through codoping Tb3+ and Gd3+ (CeF3:Gd3+,Tb3+) for viable clinical approach in the treatment of deep-seated tumors. The codoped CeF3:Gd3+,Tb3+ scintillating theranostic NPs were then coated with mesoporous silica, followed by loading with rose bengal (CGTS-RB) for later computed tomography (CT)- and magnetic resonance image (MRI)-guided X-ray stimulated synergistic radio- and photodynamic therapy (RT+XPDT) using low-dose, one-time X-ray irradiation. The results corroborated an efficient tumor regression with synergistic RT+XPDT relative to single RT. Global untargeted metabolome shifts highlighted the mechanism behind this efficient tumor regression using RT, and synergistic RT+XPDT treatment is due to the starvation of nonessential amino acids involved in protein and DNA synthesis and energy regulation pathways necessary for growth and progression. Our study also concluded that tumor and serum metabolites shift during disease progression and regression and serve as robust biomarkers for early assessment of disease state and prognosis. From our results, we propose that codoping is an effective and extendable technique to other materials for gaining high optical yield and multifunctionality and for use in diagnostic and therapeutic applications. Critically, the integration of multifunctional theranostic nanomedicines with metabolomics has excellent potential for the discovery of early metabolic biomarkers to aid in better clinical disease diagnosis and prognosis.