Label-Free Multiplex Profiling of Exosomal Proteins with a Deep Learning-Driven 3D Surround-Enhancing SERS Platform for Early Cancer Diagnosis.

Identification of protein profiling on plasma exosomes by SERS can be a promising strategy for early cancer diagnosis. However, it is still challenging to detect multiple exosomal proteins simultaneously by SERS since the Raman signals of exosomes detected by conventional colloidal nanocrystals or two-dimensional SERS substrates are incomplete and complex. Herein, we develop a novel three-dimensional (3D) surround-enhancing SERS platform, named 3D se-SERS, for the multiplex detection of exosomal proteins. In this 3D se-SERS, proteins and exosomes are covered with "hotspots" generated by the gold nanoparticles, which surround the analytes densely and three-dimensionally, providing sensitive and comprehensive SERS signals. Combining this 3D se-SERS with a deep learning model, we successfully quantitatively profiled seven proteins including CD63, CD81, CD9, CD151, CD171, TSPAN8, and PD-L1 on the surface of plasma exosomes from patients, which can predict the occurrence and advancement of lung cancer. This 3D se-SERS integrating deep learning technique benefits from high sensitivity and significant multiplexing ability for comprehensive analysis of proteins and exosomes, demonstrating the potential of deep learning-driven 3D se-SERS technology for plasma exosome-based early cancer diagnosis.

Biomimetic nanodrug blocks CD73 to inhibit adenosine and boosts antitumor immune response synergically with photothermal stimulation.

Combination of tumor immunotherapy with photothermal therapy (PTT) is a feasible tactic to overcome the drawback of immunotherapy such as poor immune response. Via triggering the immunogenic cells death (ICD), PTT can stimulate the activity of immune cells, but meanwhile, the level of adenosine is elevated via the CD73-induced decomposition of ATP which is overexpressed accompanying with the PTT process, resulting in negative feedback to impair the immune stimulation. Herein, we developed a novel biomimetic photothermal nanodrug to specifically block CD73 for inhibition of adenosine production and more efficient priming of the suppressive immune microenvironments. The nanodrug, named as AptEM@CBA, is constructed by encapsulation of photothermal agent black phosphorus quantum dots (BPQDs) and selective CD73 inhibitor α, ß-Methyleneadenosine 5'-diphosphate (AMPCP) in chitosan nanogels, which are further covered with aptamer AS1411 modified erythrocyte membrane (EM) for biomimetic camouflage. With AS1411 induced active targeting and EM induced long blood circulation time, the enrichment of the nanodrug tumor sites is promoted. The photothermal treatment promotes the maturation of dendritic cells. Meanwhile, the release of AMPCP suppress the adenosine generation via CD73 blockade, alleviating the impairment of adenosine to dendritic cells and suppressing regulatory T cells, synergically stimulate the activity of T cells. The combination of CD73 blockade with PTT, not only suppresses the growth of primary implanted tumors, but also boosts strong antitumor immunity to inhibit the growth of distal tumors, providing good potential for tumor photoimmunotherapy.

A PD-L1 targeting nanotheranostic for effective photoacoustic imaging guided photothermal-immunotherapy of tumor.

Tumor immunotherapy has been partly effective for specific cancers. However, problems such as low immune response, limited antitumor effectiveness, and high antibody costs still persist. Synergistic therapeutic approaches, such as immune checkpoint inhibition in conjunction with photothermal therapy and photoacoustic imaging, are expected to provide approaches for more precise and efficient immunotherapy of tumors. Furthermore, developing alternatives for antibodies, such as PD-L1 aptamers and nanocarriers, would reduce the cost of tumor immunotherapy. Herein, we develop a PD-L1-targeting nanotheranostic to block immune checkpoints for synergistic photothermal-immunotherapy against tumors, along with effective photoacoustic (PA) imaging. The nanotheranostic is synthesized by the modification of gold nanorods (GNRs) with the PD-L1 aptamer (APDL1), which can sensitively and specifically recognize PD-L1 on the tumor cell surface, and mediate nanoparticle accumulation and strong PA signals in tumors. The aptamer is released from GNR through a competition of glutathione (GSH) and is then functionalized as a PD-L1 blockade. In collaboration with the concurrent photothermal therapy, antitumor immunity is significantly augmented by enhancing the filtration of matured dendritic cells and suppressing regulatory T cells, followed by the activation of cytotoxic T cells and inhibition of T cell exhaustion. Such a nanotheranostic modality effectively suppresses tumor growth in mice, representing an appealing platform for both biological imaging and photoimmunotherapy of tumors.

Anti-BCMA surface engineered biomimetic photothermal nanomissile enhances multiple myeloma cell apoptosis and overcomes the disturbance of NF-κB signaling in vivo.

Conventional chemotherapy for multiple myeloma (MM) faces the challenges of a low complete remission rate and transformation to recurrence/refractory. The current MM first-line clinical drug Bortezomib (BTZ) faces the problem of enhanced tolerance and nonnegligible side effects. B cell maturation antigen (BCMA), for its important engagement in tumor signaling pathways and novel therapy technologies such as Chimeric antigen receptor T-Cell immunotherapy (CAR-T) and Antibody Drug Conjugate (ADC), has been identified as an ideal target and attracted attention in anti-MM therapy. Emerging nanotechnology provided feasible methods for drug delivery and new therapeutic strategies such as photothermal therapy (PTT). Herein, we developed a BCMA-Targeting biomimetic photothermal nanomissile BTZ@BPQDs@EM @anti-BCMA (BBE@anti-BCMA) by integration of BTZ, black phosphorus quantum dots (BPQDs), Erythrocyte membrane (EM) and BCMA antibody (anti-BCMA). We hypothesized that this engineered nanomissile could attack tumor cells in triple ways and achieve effective treatment of MM. Consequently, the intrinsic biomimetic nature of EM and the active targeting property of anti-BCMA enhanced the accumulation of therapeutic agents in the tumor site. Besides, owing to the decrease in BCMA abundance, the potential apoptosis-inducing ability was revealed. With the support of BPQDs' photothermal effect, Cleaved-Caspase-3 and Bax signal increased significantly, and the expression of Bcl-2 was inhibited. Furthermore, the synergistic photothermal/chemo therapy can effectively inhibit tumor growth and reverse the disorder of NF-κB in vivo. Importantly, this biomimetic nanodrug delivery system and antibody induced synergistic therapeutic strategy efficiently killed MM cells with ignorable systemic toxicity, which is a promising method for the future anticancer treatment of hematological malignancies in clinics.

All-Organic PTFE Coated PVDF Composite Film Exhibiting Low Conduction Loss and High Breakdown Strength for Energy Storage Applications.

Plastic film capacitors are widely used in pulse and energy storage applications because of their high breakdown strength, high power density, long lifetime, and excellent self-healing properties. Nowadays, the energy storage density of commercial biaxially oriented polypropylene (BOPP) is limited by its low dielectric constant (~2.2). Poly(vinylidene fluoride) (PVDF) exhibits a relatively high dielectric constant and breakdown strength, making it a candidate material for electrostatic capacitors. However, PVDF presents significant losses, generating a lot of waste heat. In this paper, under the guidance of the leakage mechanism, a high-insulation polytetrafluoroethylene (PTFE) coating is sprayed on the surface of a PVDF film. The potential barrier at the electrode-dielectric interface is raised by simply spraying PTFE and reducing the leakage current, and then the energy storage density is increased. After introducing the PTFE insulation coating, the high-field leakage current in the PVDF film shows an order of magnitude reduction. Moreover, the composite film presents a 30.8% improvement in breakdown strength, and a 70% enhancement in energy storage density is simultaneously achieved. The all-organic structure design provides a new idea for the application of PVDF in electrostatic capacitors.

The Role of Single Nucleotide Polymorphisms in Transporter Proteins and the Folate Metabolism Pathway in Delayed Methotrexate Excretion: A Case Report and Literature Review.

High-dose methotrexate (HDMTX) is a pivotal component of the chemotherapeutic regimens of osteosarcoma. However, the use of HDMTX is limited by an increased risk of dose-dependent toxicity. It is thought that the plasma levels and therapy-related toxicity of MTX could be associated with single nucleotide polymorphisms (SNPs) within MTX metabolism pathway genes. Here, we report a case of a paediatric osteosarcoma girl with delayed MTX excretion who was successfully managed using supportive measures and continuous veno-venous haemodiafiltration. We further identified the cause that could account for delayed elimination by genotyping analysis. The results showed that variations have been found in SLCO1B1, SLC19A1, ABCB1 and MTHFR, all those were reported to have a strong association with delayed elimination of MTX in clinical studies. After comprehensive consideration of genotype and clinical phenotype, the second course of HDMTX was administered to this patient at a half reduced dose. We also performed a literature review to summarize the pharmacogenetic factors that influence HDMTX pharmacokinetics or MTX-related adverse effects in osteosarcoma patients. It is suggested that the potential risk of delayed MTX elimination is worthy of clinical attention, and the implementation of genotyping should be considered to ensure therapeutic safety.

Optimizing thiopurine therapy in children with acute lymphoblastic leukemia: A promising "MINT" sequencing strategy and therapeutic "DNA-TG" monitoring.

Thiopurines, including thioguanine (TG), 6-mercaptopurine (6-MP), and azathioprine (AZA), are extensively used in clinical practice in children with acute lymphoblastic leukemia (ALL) and inflammatory bowel diseases. However, the common adverse effects caused by myelosuppression and hepatotoxicity limit their application. Metabolizing enzymes such as thiopurine S-methyltransferase (TPMT), nudix hydrolase 15 (NUDT15), inosine triphosphate pyrophosphohydrolase (ITPA), and drug transporters like multidrug resistance-associated protein 4 (MRP4) have been reported to mediate the metabolism and transportation of thiopurine drugs. Hence, the single nucleotide polymorphisms (SNPs) in those genes could theoretically affect the pharmacokinetics and pharmacological effects of these drugs, and might also become one of the determinants of clinical efficacy and adverse effects. Moreover, long-term clinical practices have confirmed that thiopurine-related adverse reactions are associated with the systemic concentrations of their active metabolites. In this review, we mainly summarized the pharmacogenetic studies of thiopurine drugs. We also evaluated the therapeutic drug monitoring (TDM) research studies and focused on those active metabolites, hoping to continuously improve monitoring strategies for thiopurine therapy to maximize therapeutic efficacy and minimize the adverse effects or toxicity. We proposed that tailoring thiopurine dosing based on MRP4, ITPA, NUDT15, and TMPT genotypes, defined as "MINT" panel sequencing strategy, might contribute toward improving the efficacy and safety of thiopurines. Moreover, the DNA-incorporated thioguanine nucleotide (DNA-TG) metabolite level was more suitable for red cell 6-thioguanine nucleotide (6-TGNs) monitoring, which can better predict the efficacy and safety of thiopurines. Integrating the panel "MINT" sequencing strategy with therapeutic "DNA-TG" monitoring would offer a new insight into the precision thiopurine therapy for pediatric acute lymphoblastic leukemia patients.

Assembly of Poly(ethylene glycol)ylated Oleanolic Acid on a Linear Polymer as a Pseudomucin for Influenza Virus Inhibition and Adsorption.

Biomimicry of the mucin barrier function is an efficient strategy to counteract influenza. We report the simple aminolyzation of poly(methyl vinyl ether-alt-maleic anhydride) (PM) using amine-terminated poly(ethylene glycol)ylated oleanolic acid (OAPEG) to mimic the mucin structure and its adsorption of the influenza virus. Direct interactions between influenza hemagglutinin (HA) and the prepared macromolecule evaluated by surface plasmon resonance and isothermal titration calorimetry demonstrated that the multivalent presentation of OAPEG on PM enhanced the binding affinity to HA with a decrease in KD of approximately three orders of magnitude compared with monomeric OAPEG. Moreover, hemagglutination inhibition assay, viral growth inhibition assay, and cytopathic effect reduction assay indicated that the nonglycosylated polymer could mimic natural heavily glycosylated mucin and thus promote the attachment of the virus in a subnanomolar range. Further investigation of the antiviral effects via time-of-addition assay, dynamic light scattering experiments, and transmission electron microscopy photographs indicated that the pseudomucin could adsorb the virion particles and synergistically inhibit the early attachment and final release steps of the influenza infection cycle. These findings demonstrate the effectiveness of the macromolecule in the physical sequestration and prevention of viral infection. Notably, due to its structural similarities with mucin, the biomacropolymer also has the potential for the rational design of antiviral drugs, influenza adsorbents, or filtration materials and the construction of model systems to explore protection against other pathogenic viruses.

Upregulated GATA3/miR205-5p Axis Inhibits MFNG Transcription and Reduces the Malignancy of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) accounts for approximately 20% of all breast carcinomas and has the worst prognosis of all breast cancer subtypes due to the lack of an effective target. Therefore, understanding the molecular mechanism underpinning TNBC progression could explore a new target for therapy. While the Notch pathway is critical in the development process, its dysregulation leads to TNBC initiation. Previously, we found that manic fringe (MFNG) activates the Notch signaling and induces breast cancer progression. However, the underlying molecular mechanism of MFNG upstream remains unknown. In this study, we explore the regulatory mechanisms of MFNG in TNBC. We show that the increased expression of MFNG in TNBC is associated with poor clinical prognosis and significantly promotes cell growth and migration, as well as Notch signaling activation. The mechanistic studies reveal that MFNG is a direct target of GATA3 and miR205-5p and demonstrate that GATA3 and miR205-5p overexpression attenuate MFNG oncogenic effects, while GATA3 knockdown mimics MFNG phenotype to promote TNBC progression. Moreover, we illustrate that GATA3 is required for miR205-5p activation to inhibit MFNG transcription by binding to the 3' UTR region of its mRNA, which forms the GATA3/miR205-5p/MFNG feed-forward loop. Additionally, our in vivo data show that the miR205-5p mimic combined with polyetherimide-black phosphorus (PEI-BP) nanoparticle remarkably inhibits the growth of TNBC-derived tumors which lack GATA3 expression. Collectively, our study uncovers a novel GATA3/miR205-5p/MFNG feed-forward loop as a pathway that could be a potential therapeutic target for TNBC.

Ag nanoparticles enhance immune checkpoint blockade efficacy by promoting of immune surveillance in melanoma.

Immune checkpoint blockade (ICB) therapy, represented by programmed cell death protein 1 (PD-1) and its ligand (PD-L1) monoclonal antibodies (mAbs), has shown an obvious benefit for melanoma immunotherapy, but the overall response rate is still low. To find an effective combination therapy strategy, we successfully produced small size silver nanoparticles coated with sucrose (S-AgNPs) as potent adjuvants. The antitumor effects of S-AgNPs were tested in vitro and comparatively investigated in immunodeficient and immunocompetent mice with melanoma. Fluorescence-activated cell sorting and immunofluorescent staining analysis were conducted to identify the tumor microenvironments. The expression of PD-L1 in tumors was tested by multiple methods. The combination therapy and potential toxicity of S-AgNPs and PD-1 mAbs were assessed in melanoma-bearing mice. In our findings, S-AgNPs presented potent antitumor effects, good druggability and low systemic toxicity. Functionally, we found that S-AgNPs exhibited better antitumor effects in immunocompetent mice. Mechanistically, we showed that S-AgNPs suppress tumor cell proliferation by inducing cellular apoptosis and promote cytotoxic CD8+ T cell infiltration and activity. Preclinically, S-AgNPs showed excellent local antitumor activity and mild systemic immunotoxicity with PD-1 mAbs in the inhibition of melanoma proliferation, providing a novel clinical combination treatment strategy.

Nanoscale Modification of Titanium Implants Improves Behaviors of Bone Mesenchymal Stem Cells and Osteogenesis In Vivo.

The surficial micro/nanotopography and physiochemical properties of titanium implants are essential for osteogenesis. However, these surface characters' influence on stem cell behaviors and osteogenesis is still not fully understood. In this study, titanium implants with different surface roughness, nanostructure, and wettability were fabricated by further nanoscale modification of sandblasted and acid-etched titanium (SLA: sandblasted and acid-etched) by H2O2 treatment (hSLAs: H2O2 treated SLA). The rat bone mesenchymal stem cells (rBMSCs: rat bone mesenchymal stem cells) are cultured on SLA and hSLA surfaces, and the cell behaviors of attachment, spreading, proliferation, and osteogenic differentiation are further analyzed. Measurements of surface characteristics show hSLA surface is equipped with nanoscale pores on microcavities and appeared to be hydrophilic. In vitro cell studies demonstrated that the hSLA titanium significantly enhances cell response to attachment, spreading, and proliferation. The hSLAs with proper degree of H2O2 etching (h1SLA: treating SLA with H2O2 for 1 hour) harvest the best improvement of differentiation of rBMSCs. Finally, the osteogenesis in beagle dogs was tested, and the h1SLA implants perform much better bone formation than SLA implants. These results indicate that the nanoscale modification of SLA titanium surface endowing nanostructures, roughness, and wettability could significantly improve the behaviors of bone mesenchymal stem cells and osteogenesis on the scaffold surface. These nanoscale modified SLA titanium scaffolds, fabricated in our study with enhanced cell affinity and osteogenesis, had great potential for implant dentistry.

Chemoenzymatic Synthesis of 9NHAc-GD2 Antigen to Overcome the Hydrolytic Instability of O-Acetylated-GD2 for Anticancer Conjugate Vaccine Development.

Ganglioside GD2 is an attractive tumor-associated carbohydrate antigen for anti-cancer vaccine development. However, its low immunogenicity and the significant side effects observed with anti-GD2 antibodies present significant obstacles for vaccines. To overcome these, a new GD2 derivative bearing an N-acetamide (NHAc) at its non-reducing end neuraminic acid (9NHAc-GD2) has been designed to mimic the 9-O-acetylated-GD2 (9OAc-GD2), a GD2 based antigen with a restricted expression on tumor cells. 9NHAc-GD2 was synthesized efficiently via a chemoenzymatic method and subsequently conjugated with a powerful carrier bacteriophage Qß. Mouse immunization with the Qß-9NHAc-GD2 conjugate elicited strong and long-lasting IgG antibodies, which were highly selective toward 9NHAc-GD2 with little cross-recognition of GD2. Immunization of canines with Qß-9NHAc-GD2 showed the construct was immunogenic in canines with little adverse effects, paving the way for future clinical translation to humans.

EZH2 regulates PD-L1 expression via HIF-1α in non-small cell lung cancer cells.

Lung cancer is the most commonly diagnosed cancer and accounts for most cancer-related mortalities worldwide. The high expression of programmed death ligand 1 (PD-L1) is an important factor that promotes immune escape of lung cancer, thus aggravates chemotherapy resistance and poor prognosis. Therefore, understanding the regulatory mechanism of PD-L1 in lung cancer is critical for tumor immunotherapy. Enhancer of Zeste homolog2 (EZH2), an epigenetic regulatory molecule with histone methyltransferase activity, promotes the formation of an immunosuppressive microenvironment. This study aimed to investigate the role of EZH2 in PD-L1 expression and in the progression of lung tumors. We found that EZH2 was upregulated in lung cancer tissues and positively correlated with PD-L1 levels and poor prognosis. Further, shRNA-expressing lentivirus mediated EZH2 knockdown suppressed both the mRNA and protein expression level of PD-L1, thus delaying lung cancer progression in vivo by enhancing anti-tumor immune responses. Moreover, the regulatory effect of EZH2 on PD-L1 depended on HIF-1α. The present results indicate that EZH2 regulates the immunosuppressive molecule PD-L1 expression via HIF-1α in non-small cell lung cancer cells.

Immune Landscape of Colorectal Cancer Tumor Microenvironment from Different Primary Tumor Location.

To define differences in tumor microenvironment (TME) immune phenotypes between right and left colorectal cancers (CRCs) and explore their therapeutic implications. Gene expression profiling and clinical characteristics of patients with CRC were retrieved from The Cancer Genome Atlas data portal. Immune cell infiltration was estimated based on single-sample gene set enrichment analysis. CRCs tissue microarrays (TMAs) containing 90 consecutive cases of surgical samples were used for validation. Expression of CD8A and VEGFA was confirmed by immunohistochemistry (IHC) analysis with TMAs, and overall survival (OS) was analyzed. Expression profiling data demonstrated that CRC immune microenvironment from right side tumor was characterized as increased infiltration of immune cells with enhanced cytotoxic function, based on higher cytotoxic activity scores (CYT) and interferon-γ signatures. Expression of VEGFA, which could be neutralized by bevacizumab, was associated with decreased levels of activated CD8+ T-cells, Th1 cells, and PRF1 expression on the right side, but not on the left side. IHC analysis of TMAs further confirmed an inverse correlation between CD8A and VEGFA expression, and revealed a favorable OS for patients with CD8AHiVEGFALo disease among right-side CRCs. For the left side, higher CD56bright natural killer cell infiltration and active 4-1BB/IFN-ɑ signaling, which could providing a favorable condition for cetuximab-mediated antibody-dependent cell-mediated cytotoxicity effect, was present in a cohort with extended OS. In the TME, features of immune phenotype sidedness were identified, providing an implication for differential responses to bevacizumab/cetuximab treatment. In addition, a new avenue for innovative experimental design and combinational immunotherapy to treat CRC patients was suggested.

TWIST1 upregulates miR-214 to promote epithelial-to-mesenchymal transition and metastasis in lung adenocarcinoma.

Epithelial-to-mesenchymal transition (EMT) is essential for the progression of non-invasive tumor cells into malignancy and metastasis. We found that miR-214 was increased in lung adenocarcinoma (LAD) and positively associated with metastasis, which was mediated by EMT. However, the mechanism whereby the overexpression of microRNAs (miRNAs), such as miR-214, promote EMT in LAD remains unclear. In this study, we found that TWIST1, an independent prognostic factor for overall survival, was increased in LAD and correlated positively with LAD recurrence and progression. We also found that TWIST1 contributes to the EMT process and metastasis of LAD cells. Most importantly, a positive correlation was found between the expression of miR-214 and TWIST1 in clinical LAD tissue. Additionally, miR-214 expression was decreased and its target gene suppressor of fused homolog (SUFU) was increased in LAD cells in response to the impairment of TWIST1 expression by shRNA. Overall, this study provides the first evidence to show that the high expression of TWIST1 increases the expression of miR-214 to promote the EMT process and metastasis in LAD. These findings contribute to clarify the mechanisms whereby miRNAs regulate the EMT process and implicate a new TWIST1-miR-214 pathway in the control of migration and invasion of LAD.

Improved Biocompatibility of Black Phosphorus Nanosheets by Chemical Modification.

Black phosphorus nanosheets (BPs) show great potential for various applications including biomedicine, thus their potential side effects and corresponding improvement strategy deserve investigation. Here, in vitro and in vivo biological effects of BPs with and without titanium sulfonate ligand (TiL4 ) modification are investigated. Compared to bare BPs, BPs with TiL4 modification (TiL4 @BPs) can efficiently escape from macrophages uptake, and reduce cytotoxicity and proinflammation. The corresponding mechanisms are also discussed. These findings may not only guide the applications of BPs, but also propose an efficient strategy to further improve the biocompatibility of BPs.

TiL4 -Coordinated Black Phosphorus Quantum Dots as an Efficient Contrast Agent for In Vivo Photoacoustic Imaging of Cancer.

Black phosphorus quantum dots coordinated with a sulfonic ester of the titanium ligand are prepared and exhibit enhanced stability. In vitro and in vivo photoacoustic imaging applications demonstrate that the quantum dots can efficiently accumulate inside the tumor producing tumor profiles with high spatial resolution, demonstrating their potential as an efficient agent for photoacoustic imaging.

S100B Mediates Stemness of Ovarian Cancer Stem-Like Cells Through Inhibiting p53.

S100B is one of the members of the S100 protein family and is involved in the progression of a variety of cancers. Ovarian cancer is driven by cancer stem-like cells (CSLCs) that are involved in tumorigenesis, metastasis, chemo-resistance and relapse. We then hypothesized that S100B might exert pro-tumor effects by regulating ovarian CSLCs stemness, a key characteristic of CSLCs. First, we observed the high expression of S100B in ovarian cancer specimens when compared to that in normal ovary. The S100B upregulation associated with more advanced tumor stages, poorer differentiation and poorer survival. In addition, elevated S100B expression correlated with increased expression of stem cell markers including CD133, Nanog and Oct4. Then, we found that S100B was preferentially expressed in CD133+ ovarian CSLCs derived from both ovarian cancer cell lines and primary tumors of patients. More importantly, we revealed that S100B knockdown suppressed the in vitro self-renewal and in vivo tumorigenicity of ovarian CSLCs and decreased their expression of stem cell markers. S100B ectopic expression endowed non-CSLCs with stemness, which has been demonstrated with both in vitro and in vivo experiments. Mechanically, we demonstrated that the underlying mechanism of S100B-mediated effects on CSLCs stemness was not dependent on its binding with a receptor for advanced glycation end products (RAGE), but might be through intracellular regulation, through the inhibition of p53 expression and phosphorylation. In conclusion, our results elucidate the importance of S100B in maintenance of ovarian CSLCs stemness, which might provide a promising therapeutic target for ovarian cancer. Stem Cells 2017;35:325-336.

Biodegradable black phosphorus-based nanospheres for in vivo photothermal cancer therapy.

Photothermal therapy (PTT) offers many advantages such as high efficiency and minimal invasiveness, but clinical adoption of PTT nanoagents have been stifled by unresolved concerns such as the biodegradability as well as long-term toxicity. Herein, poly (lactic-co-glycolic acid) (PLGA) loaded with black phosphorus quantum dots (BPQDs) is processed by an emulsion method to produce biodegradable BPQDs/PLGA nanospheres. The hydrophobic PLGA not only isolates the interior BPQDs from oxygen and water to enhance the photothermal stability, but also control the degradation rate of the BPQDs. The in vitro and in vivo experiments demonstrate that the BPQDs/PLGA nanospheres have inappreciable toxicity and good biocompatibility, and possess excellent PTT efficiency and tumour targeting ability as evidenced by highly efficient tumour ablation under near infrared (NIR) laser illumination. These BP-based nanospheres combine biodegradability and biocompatibility with high PTT efficiency, thus promising high clinical potential.