PPAR-γ agonists reactivate the ALDOC-NR2F1 axis to enhance sensitivity to temozolomide and suppress glioblastoma progression.

Glioblastoma (GBM) is a type of brain cancer categorized as a high-grade glioma. GBM is characterized by limited treatment options, low patient survival rates, and abnormal serotonin metabolism. Previous studies have investigated the tumor suppressor function of aldolase C (ALDOC), a glycolytic enzyme in GBM. However, it is unclear how ALDOC regulates production of serotonin and its associated receptors, HTRs. In this study, we analyzed ALDOC mRNA levels and methylation status using sequencing data and in silico datasets. Furthermore, we investigated pathways, phenotypes, and drug effects using cell and mouse models. Our results suggest that loss of ALDOC function in GBM promotes tumor cell invasion and migration. We observed that hypermethylation, which results in loss of ALDOC expression, is associated with serotonin hypersecretion and the inhibition of PPAR-γ signaling. Using several omics datasets, we present evidence that ALDOC regulates serotonin levels and safeguards PPAR-γ against serotonin metabolism mediated by 5-HT, which leads to a reduction in PPAR-γ expression. PPAR-γ activation inhibits serotonin release by HTR and diminishes GBM tumor growth in our cellular and animal models. Importantly, research has demonstrated that PPAR-γ agonists prolong animal survival rates and increase the efficacy of temozolomide in an orthotopic brain model of GBM. The relationship and function of the ALDOC-PPAR-γ axis could serve as a potential prognostic indicator. Furthermore, PPAR-γ agonists offer a new treatment alternative for glioblastoma multiforme (GBM).

Recent advances in near-infrared I/II persistent luminescent nanoparticles for biosensing and bioimaging in cancer analysis.

Photoluminescent materials (PLNs) are photoluminescent materials that can absorb external excitation light, store it, and slowly release it in the form of light in the dark to achieve long-term luminescence. Developing near-infrared (NIR) PLNs is critical to improving long-afterglow luminescent materials. Because they excite in vitro, NIR-PLNs have the potential to avoid interference from in vivo autofluorescence in biomedical applications. These materials are promising for biosensing and bioimaging applications by exploiting the near-infrared biological window. First, we discuss the biomedical applications of PLNs in the first near-infrared window (NIR-I, 700-900 nm), which have been widely developed and specifically introduce biosensors and imaging reagents. However, the light in this area still suffers from significant light scattering and tissue autofluorescence, which will affect the imaging quality. Over time, fluorescence imaging technology in the second near-infrared window (NIR-II, 1000-1700 nm) has also begun to develop rapidly. NIR-II fluorescence imaging has the advantages of low light scattering loss, high tissue penetration depth, high imaging resolution, and high signal-to-noise ratio, and it shows broad application prospects in biological analysis and medical diagnosis. This critical review collected and sorted articles from the past 5 years and introduced their respective fluorescence imaging technologies and backgrounds based on the definitions of NIR-I and NIR-II. We also analyzed the current advantages and dilemmas that remain to be solved. Herein, we also suggested specific approaches NIR-PLNs can use to improve the quality and be more applicable in cancer research.

Comprehensive Neurotoxicity of Lead Halide Perovskite Nanocrystals in Nematode Caenorhabditis elegans.

To date, all-inorganic lead halide perovskite quantum dots have emerged as promising materials for photonic, optoelectronic devices, and biological applications, especially in solar cells, raising numerous concerns about their biosafety. Most of the studies related to the toxicity of perovskite quantum dots (PeQDs) have focused on the potential risks of hybrid perovskites by using zebrafish or human cells. So far, the neurotoxic effects and fundamental mechanisms of PeQDs remain unknown. Herein, a comprehensive methodology is designed to investigate the neurotoxicity of PeQDs by using Caenorhabditis elegans as a model organism. The results show that the accumulation of PeQDs mainly focuses on the alimentary system and head region. Acute exposure to PeQDs results in a decrease in locomotor behaviors and pharyngeal pumping, whereas chronic exposure to PeQDs causes brood decline and shortens lifespan. In addition, some abnormal issues occur in the uterus during reproduction assays, such as vulva protrusion, impaired eggs left in the vulva, and egg hatching inside the mother. Excessive reactive oxygen species formation is also observed. The neurotoxicity of PeQDs is explained by gene expression. This study provides a complete insight into the neurotoxicity of PeQD and encourages the development of novel nontoxic PeQDs.

Amplification of oxidative stress by lipid surface-coated single-atom Au nanozymes for oral cancer photodynamic therapy.

Single-atom nanozymes (SANs) are the latest trend in biomaterials research and promote the application of single atoms in biological fields and the realization of protein catalysis in vivo with inorganic nanoparticles. Carbon quantum dots (CDs) have excellent biocompatibility and fluorescence properties as a substrate carrying a single atom. It is difficult to break through pure-phase single-atom materials with quantum dots as carriers. In addition, there is currently no related research in the single-atom field in the context of oral cancer, especially head and neck squamous cell carcinoma. This research developed a lipid surface-coated nanozyme combined with CDs, single-atomic gold, and modified lipid ligands (DSPE-PEG) with transferrin (Tf) to treat oral squamous cell carcinoma. The study results have demonstrated that surface-modified single-atom carbon quantum dots (m-SACDs) exhibit excellent therapeutic effects and enable in situ image tracking for diagnosing and treating head and neck squamous carcinoma (HNSCC).

Sustaining the Activation of EGFR Signal by Inflammatory Cytokine IL17A Prompts Cell Proliferation and EGFR-TKI Resistance in Lung Cancer.

Non-small-cell lung cancer (NSCLC) is a typical inflammation-associated cancer, and lung adenocarcinoma (LUAD) is the most common pathological subtype. Epidermal growth factor (EGF) receptor (EGFR) mutations are the most common driver mutations of LUAD, and they have been identified as important therapeutic targets by EGFR-tyrosine kinase inhibitors (TKIs). The proinflammatory cytokine, interleukin (IL)-17A, and IL-17A-producing cells were reported to be elevated in the tumor microenvironment and peripheral blood of NSCLC patients and to be correlated with tumor progression and poor prognoses. However, the pathophysiological role of IL-17A in NSCLC remains unclear, although some studies suggested its involvement in cancer cell invasion and metastasis. Herein, we observed that expressions of IL-17A and its receptor, IL-17 receptor C (IL-17RC), were elevated in LUAD tissues and were correlated with poor survival in different lung cancer cohorts. In LUAD cells with mutant EGFR, the IL-17A/IL-17RC axis was shown to enhance phosphorylation of EGFR and Met, thereby promoting proliferation and resistance to EGFR-TKIs such as afatinib. In LUAD cells with wild-type (WT) EGFR, we found that the IL-17A/IL-17RC axis enhanced EGF-induced EGFR activation and cell proliferation through causing impairment of EGF-induced EGFR lysosomal degradation. Collectively, our results indicated diverse impacts of the IL-17A/IL-17RC axis on EGFR activation in LUAD cells with WT and mutant EGFR and suggested that developing therapeutic strategies against IL-17A/IL-17RC would be valuable for LUAD treatment.

Detecting intragenic trans-splicing events from non-co-linearly spliced junctions by hybrid sequencing.

Trans-spliced RNAs (ts-RNAs) are a type of non-co-linear (NCL) transcripts that consist of exons in an order topologically inconsistent with the corresponding DNA template. Detecting ts-RNAs is often interfered by experimental artifacts, circular RNAs (circRNAs) and genetic rearrangements. Particularly, intragenic ts-RNAs, which are derived from separate precursor mRNA molecules of the same gene, are often mistaken for circRNAs through analyses of RNA-seq data. Here we developed a bioinformatics pipeline (NCLscan-hybrid), which integrated short and long RNA-seq reads to minimize false positives and proposed out-of-circle and rolling-circle long reads to distinguish between intragenic ts-RNAs and circRNAs. Combining NCLscan-hybrid screening and multiple experimental validation steps successfully confirmed that four NCL events, which were previously regarded as circRNAs in databases, originated from trans-splicing. CRISPR-based endogenous genome modification experiments further showed that flanking intronic complementary sequences can significantly contribute to ts-RNA formation, providing an efficient/specific method to deplete ts-RNAs. We also experimentally validated that one ts-RNA (ts-ARFGEF1) played an important role for p53-mediated apoptosis through affecting the PERK/eIF2a/ATF4/CHOP signaling pathway in breast cancer cells. This study thus described both bioinformatics procedures and experimental validation steps for rigorous characterization of ts-RNAs, expanding future studies for identification, biogenesis, and function of these important but understudied transcripts.

Glucose transporter 4: Insulin response mastermind, glycolysis catalyst and treatment direction for cancer progression.

The glucose transporter family (GLUT) consists of fourteen members. It is responsible for glucose homeostasis and glucose transport from the extracellular space to the cell cytoplasm to further cascade catalysis. GLUT proteins are encoded by the solute carrier family 2 (SLC2) genes and are members of the major facilitator superfamily of membrane transporters. Moreover, different GLUTs also have their transporter kinetics and distribution, so each GLUT member has its uniqueness and importance to play essential roles in human physiology. Evidence from many studies in the field of diabetes showed that GLUT4 travels between the plasma membrane and intracellular vesicles (GLUT4-storage vesicles, GSVs) and that the PI3K/Akt pathway regulates this activity in an insulin-dependent manner or by the AMPK pathway in response to muscle contraction. Moreover, some published results also pointed out that GLUT4 mediates insulin-dependent glucose uptake. Thus, dysfunction of GLUT4 can induce insulin resistance, metabolic reprogramming in diverse chronic diseases, inflammation, and cancer. In addition to the relationship between GLUT4 and insulin response, recent studies also referred to the potential upstream transcription factors that can bind to the promoter region of GLUT4 to regulating downstream signals. Combined all of the evidence, we conclude that GLUT4 has shown valuable unknown functions and is of clinical significance in cancers, which deserves our in-depth discussion and design compounds by structure basis to achieve therapeutic effects. Thus, we intend to write up a most updated review manuscript to include the most recent and critical research findings elucidating how and why GLUT4 plays an essential role in carcinogenesis, which may have broad interests and impacts on this field.

The activation of EP300 by F11R leads to EMT and acts as a prognostic factor in triple-negative breast cancers.

Cancer progression is influenced by junctional adhesion molecule (JAM) family members. The relationship between JAM family members and different types of cancer was examined using The Cancer Genome Atlas dataset. mRNA levels of the F11R (F11 receptor) in tumours were inversely correlated to the expression of JAM-2 and JAM-3. This relationship was unique to breast cancer (BCa) and was associated with poor prognosis (p = 0.024, hazard ratio = 1.44 [1.05-1.99]). A 50-gene molecular signature (prediction analysis of microarray 50) was used to subtype BCa. F11R mRNA expression significantly increased in human epidermal growth factor receptor 2 (HER2)-enriched (p = 0.0035) and basal-like BCa tumours (p = 0.0005). We evaluated F11R protein levels in two different compositions of BCa subtype patient tissue array cohorts to determine the relationship between BCa subtype and prognosis. Immunohistochemistry staining revealed that a high F11R protein level was associated with poor overall survival (p < 0.001; Taipei Medical University [TMU] cohort, p < 0.001; Kaohsiung Veterans General Hospital [KVGH] cohort) or disease-free survival (p < 0.001 [TMU cohort], p = 0.034 [KVGH cohort]) in patients with BCa. Comparison of F11R levels in different subtypes revealed the association of poor prognosis with high levels of F11R among luminal (p < 0.001 [TMU cohort], p = 0.027 [KVGH cohort]), HER2 positive (p = 0.018 [TMU cohort], p = 0.037 [KVGH cohort]), and triple-negative (p = 0.013 [TMU cohort], p = 0.037 [KVGH cohort]) BCa. F11R-based RNA microarray analysis and Ingenuity Pathway Analysis were successful in profiling the detailed gene ontology of triple-negative BCa cells regulated by F11R. The EP300 transcription factor was highly correlated with F11R in BCa (R = 0.51, p < 0.001). By analysing these F11R-affected molecules with the L1000CDs datasets, we were able to predict some repurposing drugs for potential application in F11R-positive BCa treatment.

The cytoplasmic expression of FSTL3 correlates with colorectal cancer progression, metastasis status and prognosis.

Follistatin-like (FSTL) family members are associated with cancer progression. However, differences between FSTL members with identical cancer types have not been systematically investigated. Among the most malignant tumours worldwide, colorectal cancer (CRC) has high metastatic potential and chemoresistance, which makes it challenging to treat. A systematic examination of the relationship between the expression of FSTL family members in CRC will provide valuable information for prognosis and therapeutic development. Based on large cohort survival analyses, we determined that FSTL3 was associated with a significantly worse prognosis in CRC at the RNA and protein levels. Immunohistochemistry staining of CRC specimens revealed that FSTL3 expression levels in the cytosol were significantly associated with a poor prognosis in terms of overall and disease-free survival. Molecular simulation analysis showed that FSTL3 participated in multiple cell motility signalling pathways via the TGF-ß1/TWIST1 axis to control CRC metastasis. The findings provide evidence of the significance of FSTL3 in the oncogenesis and metastasis of CRC. FSTL3 may be useful as a diagnostic or prognostic biomarker, and as a potential therapeutic target.

Overexpression of synaptic vesicle protein Rab GTPase 3C promotes vesicular exocytosis and drug resistance in colorectal cancer cells.

Rab GTPase 3C (RAB3C) is a peripheral membrane protein that is involved in membrane trafficking (vesicle formation) and cell movement. Recently, researchers have noted the exocytosis of RAB proteins, and their dysregulation is correlated with drug resistance and the altered tumor microenvironment in tumorigenesis. However, the molecular mechanisms of exocytotic RABs in the carcinogenicity of colorectal cancer (CRC) remain unknown. Researchers have used various in silico datasets to evaluate the expression profiles of RAB family members. We confirmed that RAB3C plays a key role in CRC progression. Its overexpression promotes exocytosis and is related to the resistance to several chemotherapeutic drugs. We established a proteomic dataset based on RAB3C, and found that dystrophin is one of the proteins that is upregulated with the overexpression of RAB3C. According to our results, RAB3C-induced dystrophin expression promotes vesicle formation and packaging. A connectivity map predicted that the cannabinoid receptor 2 (CB2) agonists reverse RAB3C-associated drug resistance, and that these agonists have synergistic effects when combined with standard chemotherapy regimens. Moreover, we found high dystrophin expression levels in CRC patients with poor survival outcomes. A combination of the dystrophin and RAB3C expression profiles can serve as an independent prognostic factor in CRC and is associated with several clinicopathological parameters. In addition, the RAB3C-dystrophin axis is positively correlated with the phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) genetic alterations in CRC patients. These findings can be used to provide novel combined therapeutic options for the treatment of CRC.

Gold Nanoparticles as a Biosensor for Cancer Biomarker Determination.

Molecular biology applications based on gold nanotechnology have revolutionary impacts, especially in diagnosing and treating molecular and cellular levels. The combination of plasmonic resonance, biochemistry, and optoelectronic engineering has increased the detection of molecules and the possibility of atoms. These advantages have brought medical research to the cellular level for application potential. Many research groups are working towards this. The superior analytical properties of gold nanoparticles can not only be used as an effective drug screening instrument for gene sequencing in new drug development but also as an essential tool for detecting physiological functions, such as blood glucose, antigen-antibody analysis, etc. The review introduces the principles of biomedical sensing systems, the principles of nanomaterial analysis applied to biomedicine at home and abroad, and the chemical surface modification of various gold nanoparticles.

Iron-Based Ceramic Composite Nanomaterials for Magnetic Fluid Hyperthermia and Drug Delivery.

Because of the unique physicochemical properties of magnetic iron-based nanoparticles, such as superparamagnetism, high saturation magnetization, and high effective surface area, they have been applied in biomedical fields such as diagnostic imaging, disease treatment, and biochemical separation. Iron-based nanoparticles have been used in magnetic resonance imaging (MRI) to produce clearer and more detailed images, and they have therapeutic applications in magnetic fluid hyperthermia (MFH). In recent years, researchers have used clay minerals, such as ceramic materials with iron-based nanoparticles, to construct nanocomposite materials with enhanced saturation, magnetization, and thermal effects. Owing to their unique structure and large specific surface area, iron-based nanoparticles can be homogenized by adding different proportions of ceramic minerals before and after modification to enhance saturation magnetization. In this review, we assess the potential to improve the magnetic properties of iron-based nanoparticles and in the preparation of multifunctional composite materials through their combination with ceramic materials. We demonstrate the potential of ferromagnetic enhancement and multifunctional composite materials for MRI diagnosis, drug delivery, MFH therapy, and cellular imaging applications.

The CHST11 gene is linked to lung cancer and pulmonary fibrosis.

BACKGROUND: The abnormal modification of chondroitin sulfate is one of the leading causes of disease, including cancer progression. During chondroitin sulfate biosynthesis, the CHST11 enzyme plays a vital role in its modification, but its role in cancer is not fully understood. Therefore, understanding the relationship between CHST11 and pulmonary-related diseases through clinically relevant information may be useful for diagnosis or treatment. METHODS: A variety of pulmonary fibrosis clinical gene expression omnibus (GEO) datasets were used to assess the association between CHST11-related manifestations and fibrosis. Multiple lung cancer-related databases, including The Cancer Genome Atlas, GEO datasets, UCSC Xena, GEPIA2, Cbioportal and ingenuity pathway analysis were used to evaluate the clinical correlation between CHST11 and lung cancer and potential molecular mechanisms. For drug repurposing prediction, the molecules that correlated with CHST11 were subjected to the LINCS L1000 algorithm. A variety of in vitro assays were performed to evaluate the in-silico models, including RNA and protein expression, proliferation, migration and invasion. RESULTS: Clinical analyses indicate that the levels of CHST11 are significantly elevated in cases of pulmonary-related diseases, including fibrosis and lung cancer. According to multiple lung cancer cohorts, CHST11 is the only member of the carbohydrate sulfotransferase family associated with overall survival for lung adenocarcinomas, and it is highly related to smoking-induced lung cancer patients. Based on the results of in vitro experiments, CHST11 expression contributes to tumor malignancy and promotes multiple fibrotic activators. Correlation-based ingenuity pathway analysis indicated that CHST11-related molecules contributed to pulmonary fibrosis or lung adenocarcinomas via similar upstream stimulators. Based on known molecular regulatory relationships, CHST11 has been associated with the regulation of TGF-ß and INFγ as important molecules contributing to fibrosis and cancer progression. Interestingly, WordCloud analysis revealed that CHST11-related molecules are involved in regulation primarily by integrin signaling, and these relationships were consistently reflected in the analysis of cell lines and the clinical correlation. A CHST11 signature-based drug repurposing analysis demonstrated that the CHST11/integrin axis could be targeted by AG-1478 (Tyrphostin AG 1478), brefeldin A, geldanamycin and importazole. CONCLUSIONS: This study provides the first demonstration that CHST11 may be used as a biomarker for pulmonary fibrosis or lung cancer, and the levels of CHST11 were increased by TGF-ß and INFγ. The molecular simulation analyses demonstrate that the CHST11/integrin axis is a potential therapeutic target for treating lung cancer.

Novel monodisperse FePt nanocomposites for T2-weighted magnetic resonance imaging: biomedical theranostics applications.

Given the high incidence and mortality of cancer, current research is focused on designing efficient diagnostic methods. At present, clinical diagnoses are made based on X-ray, computed tomography, magnetic resonance imaging (MRI), ultrasound, and fiber optic endoscopy. MRI is a powerful diagnostic tool because it is non-invasive, has a high spatial resolution, uses non-ionizing radiation, and has good soft-tissue contrast. However, the long relaxation time of water protons may result in the inability to distinguish different tissues. To overcome this drawback of MRI, magnetic resonance contrast agents can enhance the contrast, improve the sensitivity of MRI-based diagnoses, increase the success rate of surgery, and reduce tumor recurrence. This review focuses on using iron-platinum (FePt) nanoparticles (NPs) in T2-weighted MRI to detect tumor location based on dark-field changes. In addition, existing methods for optimizing and improving FePt NPs are reviewed, and the MRI applications of FePt NPs are discussed. FePT NPs are expected to strengthen MRI resolution, thereby helping to inhibit tumor development.

Ultrasound and Nanomedicine for Cancer-Targeted Drug Delivery: Screening, Cellular Mechanisms and Therapeutic Opportunities.

Cancer is a disease characterized by abnormal cell growth. According to a report published by the World Health Organization (WHO), cancer is the second leading cause of death globally, responsible for an estimated 9.6 million deaths in 2018. It should be noted that ultrasound is already widely used as a diagnostic procedure for detecting tumorigenesis. In addition, ultrasound energy can also be utilized effectively for treating cancer. By filling the interior of lipospheres with gas molecules, these particles can serve both as contrast agents for ultrasonic imaging and as delivery systems for drugs such as microbubbles and nanobubbles. Therefore, this review aims to describe the nanoparticle-assisted drug delivery system and how it can enhance image analysis and biomedicine. The formation characteristics of nanoparticles indicate that they will accumulate at the tumor site upon ultrasonic imaging, in accordance with their modification characteristics. As a result of changing the accumulation of materials, it is possible to examine the results by comparing images of other tumor cell lines. It is also possible to investigate ultrasound images for evidence of cellular effects. In combination with a precision ultrasound imaging system, drug-carrying lipospheres can precisely track tumor tissue and deliver drugs to tumor cells to enhance the ability of this nanocomposite to treat cancer.

Regorafenib inhibits epithelial-mesenchymal transition and suppresses cholangiocarcinoma metastasis via YAP1-AREG axis.

Cholangiocarcinoma (CCA) is a subtype of bile duct cancer usually diagnosed late with a low survival rate and no satisfactorily systemic treatment. Recently, regorafenib has been accepted as a second-line treatment for CCA patients. In this study, we investigated the potential signal transduction pathways mediated by regorafenib. We established a transcriptomic database for regorafenib-treated CCA cells using expression microarray chips. Our data indicate that regorafenib inhibits yes-associated protein 1 (YAP1) activity in various CCA cells. In addition, we demonstrated that YAP1 regulates epithelial-mesenchymal transition (EMT)-related genes, including E-cadherin and SNAI2. We further examined YAP1 activity, phosphorylation status, and expression levels of YAP1 downstream target genes in the regorafenib model. We found that regorafenib dramatically suppressed these events in CCA cells. Moreover, in vivo results revealed that regorafenib could significantly inhibit lung foci formation and tumorigenicity. Most importantly, regorafenib and amphiregulin (AREG) neutralize antibody exhibited synergistic effects against CCA cells. In a clinical setting, patients with high YAP1 and EMT expression had a worse survival rate than patients with low YAP1, and EMT expression did. In addition, we found that YAP1 upregulated the downstream target amphiregulin in CCA. Our findings suggest that AREG neutralizing antibody antibodies combined with regorafenib can reverse the CCA metastatic phenotype and EMT in vitro and in vivo. These findings provide novel therapeutic strategies to combat the metastasis of CCA.

The role of fructose 1,6-bisphosphate-mediated glycolysis/gluconeogenesis genes in cancer prognosis.

Metabolic reprogramming and elevated glycolysis levels are associated with tumor progression. However, despite cancer cells selectively inhibiting or expressing certain metabolic enzymes, it is unclear whether differences in gene profiles influence patient outcomes. Therefore, identifying the differences in enzyme action may facilitate discovery of gene ontology variations to characterize tumors. Fructose-1,6-bisphosphate (F-1,6-BP) is an important intermediate in glucose metabolism, particularly in cancer. Gluconeogenesis and glycolysis require fructose-1,6-bisphosphonates 1 (FBP1) and fructose-bisphosphate aldolase A (ALDOA), which participate in F-1,6-BP conversion. Increased expression of ALDOA and decreased expression of FBP1 are associated with the progression of various forms of cancer in humans. However, the exact molecular mechanism by which ALDOA and FBP1 are involved in the switching of F-1,6-BP is not yet known. As a result of their pancancer pattern, the relationship between ALDOA and FBP1 in patient prognosis is reversed, particularly in lung adenocarcinoma (LUAD) and liver hepatocellular carcinoma (LIHC). Using The Cancer Genome Atlas (TCGA), we observed that FBP1 expression was low in patients with LUAD and LIHC tumors, which was distinct from ALDOA. A similar trend was observed in the analysis of Cancer Cell Line Encyclopedia (CCLE) datasets. By dissecting downstream networks and possible upstream regulators, using ALDOA and FBP1 as the core, we identified common signatures and interaction events regulated by ALDOA and FBP1. Notably, the identified effectors dominated by ALDOA or FBP1 were distributed in opposite patterns and can be considered independent prognostic indicators for patients with LUAD and LIHC. Therefore, uncovering the effectors between ALDOA and FBP1 will lead to novel therapeutic strategies for cancer patients.

The optical research progress of nanophosphors composed of transition elements in the fourth period of near-infrared windows I and II for deep-tissue theranostics.

Research in the field of nano-optics is advancing by leaps and bounds, among which near-infrared (NIR) light optics have attracted much attention. NIR light has a longer wavelength than visible light, such that it can avoid shielding caused by biological tissues. This advantage has driven its importance and practicality in human treatment applications and has attracted significant attention from researchers in academia and industry. In the broad spectrum of infrared light wavelengths, the most noticeable ones are the NIR biological window I of 700-900 nm and window II of 1000-1700 nm. Luminescent materials can effectively cover the NIR biological window with different doping strategies. These doped elements are mostly transition elements with multielectron orbitals. Several nanomaterials based on narrow-spectrum lanthanides have been developed to correspond to biological applications of different wavelengths. However, this review explicitly introduces the absorption and reflection/luminescence interactions between NIR light and biological tissues independently. Unlike the adjustment of the wavelength of the lanthanide series, this review analyzes the NIR optical properties of the fourth-period element ions in transition elements (such as Cr3+ and Ni2+). These elements have a broadband wavelength of NIR light emission and higher quantum efficiency, corresponding to the absorption and emission spectrum and photobiological absorption of different NIR windows for therapeutic diagnosis. Finally, this review lists and explores other broadband NIR phosphors and has tried to discover the possibility of non-invasive precision medicine in the future.

Progress and Viewpoints of Multifunctional Composite Nanomaterials for Glioblastoma Theranostics.

The most common malignant tumor of the brain is glioblastoma multiforme (GBM) in adults. Many patients die shortly after diagnosis, and only 6% of patients survive more than 5 years. Moreover, the current average survival of malignant brain tumors is only about 15 months, and the recurrence rate within 2 years is almost 100%. Brain diseases are complicated to treat. The reason for this is that drugs are challenging to deliver to the brain because there is a blood-brain barrier (BBB) protection mechanism in the brain, which only allows water, oxygen, and blood sugar to enter the brain through blood vessels. Other chemicals cannot enter the brain due to their large size or are considered harmful substances. As a result, the efficacy of drugs for treating brain diseases is only about 30%, which cannot satisfy treatment expectations. Therefore, researchers have designed many types of nanoparticles and nanocomposites to fight against the most common malignant tumors in the brain, and they have been successful in animal experiments. This review will discuss the application of various nanocomposites in diagnosing and treating GBM. The topics include (1) the efficient and long-term tracking of brain images (magnetic resonance imaging, MRI, and near-infrared light (NIR)); (2) breaking through BBB for drug delivery; and (3) natural and chemical drugs equipped with nanomaterials. These multifunctional nanoparticles can overcome current difficulties and achieve progressive GBM treatment and diagnosis results.

Integrated therapy platform of exosomal system: hybrid inorganic/organic nanoparticles with exosomes for cancer treatment.

Recent studies have found that exosomes or extracellular vehicles (EVs) are associated with cancer metastasis, disease progression, diagnosis, and treatment, leading to a rapidly emerging area of exocrine vesicle research. Relying on the superior targeting function and bio-compatibility of exosomes, researchers have been able to deliver drugs to cancer stem cells deep within tumors in mouse models. Despite significant efforts made in this relatively new field of exosome research, progress has been held back by challenges such as inefficient separation methods, difficulties in characterization/tracking, and a lack of specific biomarkers. Therefore, current researches are devoted to combining nanomaterials with exosomes to improve these shortcomings. Adding inorganic/organic nanoparticles such as artificial liposomes and iron oxide can bring more drug options and various fluorescent or magnetic diagnostic possibilities to the exosome system. Moreover, the applications of exosomes need to be further evaluated under actual physiological conditions. This review article highlights the potential of exosome-biomimetic nanoparticles for their use as drug carriers to improve the efficacy of anticancer therapy.