Search

Aim: To investigate Prussian blue nanoparticles (PBNPs) coated with the synthetic analog of dsRNA polyinosinic-polycytidylic acid (polyIC) for their ability to function as HIV latency reversing agents. Methods: A layer-by-layer method was used to synthesize polyIC-coated PBNPs (polyIC-PBNPs). PolyIC-PBNPs were stable and monodisperse, maintained the native absorbance properties of both polyIC and PBNPs and were obtained with high nanoparticle collection yield and polyIC attachment efficiencies. Results: PolyIC-PBNPs were more effective in reactivating latent HIV than free polyIC in a cell model of HIV latency. Furthermore, polyIC-PBNPs were more effective in promoting immune activation than free polyIC in CD4 and CD8 T cells. Conclusion: PBNPs function as efficient carriers of nucleic acids to directly reverse HIV latency and enhance immune activation.

Fig Supp 2

Supplementary methods and tables

Fig Supp 3

Fig Supp 7

Fig Supp 5

Despite the outstanding clinical results of immune checkpoint blockade (ICB) in melanoma and other cancers, clinical trials in breast cancer have reported low responses to these therapies. Current efforts are now focused on improving the treatment efficacy of ICB in breast cancer using new combination designs such as molecularly targeted agents, including histone deacetylase inhibitors (HDACi). These epigenetic drugs have been widely described as potent cytotoxic agents for cancer cells. In this work, we report new noncanonical regulatory properties of ultra-selective HDAC6i over the expression and function of epithelial–mesenchymal transition pathways and the invasiveness potential of breast cancer. These unexplored roles position HDAC6i as attractive options to potentiate ongoing immunotherapeutic approaches. These new functional activities of HDAC6i involved regulation of the E-cadherin/STAT3 axis. Pretreatment of tumors with HDAC6i induced critical changes in the tumor microenvironment, resulting in improved effectiveness of ICB and preventing dissemination of cancer cells to secondary niches. Our results demonstrate for the first time that HDAC6i can both improve ICB antitumor immune responses and diminish the invasiveness of breast cancer with minimal cytotoxic effects, thus departing from the cytotoxicity-centric paradigm previously assigned to HDACi.Significance:Ultraselective HDAC6 inhibitors can reduce tumor growth and invasiveness of breast cancer by noncanonical mechanisms unrelated to the previously cytotoxic properties attributed to HDAC inhibitors.

Purpose:The ability of natural killer (NK) cells to lyse allogeneic targets, without the need for explicit matching or priming, makes them an attractive platform for cell-based immunotherapy. Umbilical cord blood is a practical source for generating banks of such third-party NK cells for “off-the-shelf” cell therapy applications. NK cells are highly cytolytic, and their potent antitumor effects can be rapidly triggered by a lack of HLA expression on interacting target cells, as is the case for a majority of solid tumors, including neuroblastoma. Neuroblastoma is a leading cause of pediatric cancer–related deaths and an ideal candidate for NK-cell therapy. However, the antitumor efficacy of NK cells is limited by immunosuppressive cytokines in the tumor microenvironment, such as TGFβ, which impair NK cell function and survival.Experimental Design:To overcome this, we genetically modified NK cells to express variant TGFβ receptors, which couple a mutant TGFβ dominant-negative receptor to NK-specific activating domains. We hypothesized that with these engineered receptors, inhibitory TGFβ signals are effectively converted to activating signals.Results:Modified NK cells exhibited higher cytotoxic activity against neuroblastoma in a TGFβ-rich environment in vitro and superior progression-free survival in vivo, as compared with their unmodified controls.Conclusions:Our results support the development of “off-the-shelf” gene-modified NK cells, that overcome TGFβ-mediated immune evasion, in patients with neuroblastoma and other TGFβ-secreting malignancies.

Fig Supp 4

Supplementary Table 1: NK cell persistence. Fig. S1. Characterizing SHSY5Y neuroblastoma. Fig. S2. NK cell functionality against HTLA230 neuroblastoma. Fig. S3. Verification of NK Cell Sorting. Fig. S4. NK Cell Phenotype and Proliferation. Fig. S5. NK cell phenotype following TGFbeta exposure. Fig. S6. Neuroblastoma tumor progression and the correlation between progression-free survival and NK cell persistence. Fig. S7. NK cell detection in neuroblastoma-bearing mice. Supplementary Materials and Methods.

Fig Supp 1

Fig Supp 6

Wound Assay vehicle

Despite the promise of immunotherapy such as the immune checkpoint inhibitors (ICIs) anti-PD-1 and anti-CTLA-4 for advanced melanoma, only 26%–52% of patients respond, and many experience grade III/IV immune-related adverse events. Motivated by the need for an effective therapy for patients non-responsive to clinically approved ICIs, we have developed a novel nanoimmunotherapy that combines locally administered Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) with systemically administered agonistic anti-CD137 monoclonal antibody therapy (aCD137). PBNP-PTT was administered at various thermal doses to melanoma cells in vitro, and was combined with aCD137 in vivo to test treatment effects on melanoma tumor progression, animal survival, immunological protection against tumor rechallenge, and hepatotoxicity. When administered at a melanoma-specific thermal dose, PBNP-PTT elicits immunogenic cell death (ICD) in melanoma cells and upregulates markers associated with antigen presentation and immune cell co-stimulation in vitro. Consequently, PBNP-PTT eliminates primary melanoma tumors in vivo, yielding long-term tumor-free survival. However, the antitumor immune effects generated by PBNP-PTT cannot eliminate secondary tumors, despite significantly slowing their growth. The addition of aCD137 enables significant abscopal efficacy and improvement of survival, functioning through activated dendritic cells and tumor-infiltrating CD8(+) T cells, and generates CD4(+) and CD8(+) T cell memory that manifests in the rejection of tumor rechallenge, with no long-term hepatotoxicity. This study describes for the first time a novel and effective nanoimmunotherapy combination of PBNP-PTT with aCD137 mAb therapy for melanoma.

Tumor-associated macrophages (TAMs) play a critical role in shaping the tumor microenvironment (TME). Responding to numerous cues from various cell types present in the tumor, TAMs often exhibit a spectrum of phenotypes, often ranging between M1 (inflammatory) and M2 (tumor-supportive) macrophages. Therefore, the M1/M2 macrophage ratio often determines tumor suppression or tumor growth. Higher TAMs infiltration is usually associated with poor prognosis in several cancer types due to their predisposition towards M2 function. Therefore, reprogramming TAMs to the M1 phenotype is a promising avenue to be explored. In this study, we reprogrammed bone marrow-derived macrophages (BMDMs) ex-vivo by treating them with HDAC6 inhibitor (HDAC6i) followed by polarization to M1 phenotype and directly implanted them into immunocompetent tumors. We performed immunohistochemistry of tumors for macrophage markers, immunophenotyping of tumor-infiltrated immune cells by flow cytometry, gene expression analysis by quantitative PCR, and immunoblot analyses. We also performed single-cell analyses, including secretome with Isoplexis platform and CD45+ tumor-infiltrated immune cells by single-cell RNA-seq analysis. To further underscore the translatability of macrophage-based cell therapy, we treated humanized NSG-SGM3 mice bearing melanoma PDX tumors with HDAC6i-treated human M1 macrophages. Adoptive cell therapy (ACT) with HDAC6i-treated M1 macrophages resulted in significant tumor suppression and prolonged survival compared to other cohorts in the study. Two weeks post-transplantation, ACT macrophages were viable, and inhibition of HDAC6 rendered them resistant to M2 polarization. Inhibition of HDAC6 suppressed STAT3 activation and subsequent M2 marker Arg1 expression, further underscoring the role of HDAC6 in macrophage plasticity. M2 re-polarization assay further corroborated that HDAC6i-treated M1 macrophages were resistant to change into M2 phenotype. Single-cell secretome analysis revealed polyfunctionality as HDAC6-treated M1 macrophages were capable of secreting inflammatory cytokines such as Tnfa and t-cell recruiting Cxcl10. Histological analysis of tumor sections for macrophage markers and single-cell transcriptomic analysis of tumor-infiltrated immune cells further corroborated the M1/M2 ratio the increase observed by flow cytometry. Pro-inflammatory gene expression signature from scRNA-seq analysis also correlated with better survival in the SKCM dataset. In both immuno-competent SM1 murine melanoma and humanized NSG-SGM3 melanoma models, ACT enhanced anti-tumor immunity by increasing the M1/M2 ratio and infiltration of CD8 effector T-cells shifting the balance towards anti-tumor immunity. For the first time, we demonstrate that reprogramming macrophages with class-specific HDAC inhibitors is a viable cell therapy option to treat solid tumors. Citation Format: Satish Kumar Reddy Noonepalle, Maria Gracia Hernandez, Christian Zevallos Delgado, Nima Aghdam, Nithya Gajendran, Tessa Knox, Karen Tan, Eduardo Sotomayor, Katherine B. Chiappinelli, Duncan Wardrop, Anelia Horvath, Brett A. Shook, Norman Lee, Anatoly Dritschilo, Rohan Fernandes, Maho Shibata, Karthik Musunuri, Alejandro Villagra. Reprogramming macrophages with HDAC6 inhibitors for anti-cancer macrophage-based cell therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 900.

Photothermal therapy (PTT) is an effective method for tumor eradication and has been successfully combined with immunotherapy. However, besides its cytotoxic effects, little is known about the effect of the PTT thermal dose on the immunogenicity of treated tumor cells. Therefore, we administered a range of thermal doses using Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) and assessed their effects on tumor cell death and concomitant immunogenicity correlates in two human neuroblastoma cell lines: SH-SY5Y (MYCN-non-amplified) and LAN-1 (MYCN-amplified). PBNP-PTT generated thermal dose-dependent tumor cell killing and immunogenic cell death (ICD) in both tumor lines in vitro. However, the effect of the thermal dose on ICD and the expression of costimulatory molecules, immune checkpoint molecules, major histocompatibility complexes, an NK cell-activating ligand, and a neuroblastoma-associated antigen were significantly more pronounced in SH-SY5Y cells compared with LAN-1 cells, consistent with the high-risk phenotype of LAN-1 cells. In functional co-culture studies in vitro, T cells exhibited significantly higher cytotoxicity toward SH-SY5Y cells relative to LAN-1 cells at equivalent thermal doses. This preliminary report suggests the importance of moving past the traditional focus of using PTT solely for tumor eradication to one that considers the immunogenic effects of PTT thermal dose to facilitate its success in cancer immunotherapy.

Natural killer (NK) cells are attractive effector cells of the innate immune system against human immunodeficiency virus (HIV) and cancer. However, NK cell therapies are limited by the fact that target cells evade NK cells, for example, in latent reservoirs (in HIV) or through upregulation of inhibitory signals (in cancer). To address this limitation, we describe a biodegradable nanoparticle-based “priming” approach to enhance the cytotoxic efficacy of peripheral blood mononuclear cell-derived NK cells. We present poly(lactic-co-glycolic acid) (PLGA) nanodepots (NDs) that co-encapsulate prostratin, a latency-reversing agent, and anti-CD25 (aCD25), a cell surface binding antibody, to enhance primary NK cell function against HIV and cancer. We utilize a nanoemulsion synthesis scheme to encapsulate both prostratin and aCD25 within the PLGA NDs (termed Pro-aCD25-NDs). Physicochemical characterization studies of the NDs demonstrated that our synthesis scheme resulted in stable and monodisperse Pro-aCD25-NDs. The NDs successfully released both active prostratin and anti-CD25, and with controllable release kinetics. When Pro-aCD25-NDs were administered in an in vitro model of latent HIV and acute T cell leukemia using J-Lat 10.6 cells, the NDs were observed to prime J-Lat cells resulting in significantly increased NK cell-mediated cytotoxicity compared to free prostratin plus anti-CD25, and other controls. These findings demonstrate the feasibility of using our Pro-aCD25-NDs to prime target cells for enhancing the cytotoxicity of NK cells as antiviral or antitumor agents.

Three material engineering strategies in the form of doping (Boron-doping), nanostructuring (nanosheet (NS) formation) and decorating with plasmonic nanoparticles (loading with Ag metal), were integrated to improve the photocatalytic activity of graphitic carbon nitride (gC3N4). Concentrations of B-doping and Ag-loading were optimized to maximize the catalytic performance in the final nanocomposite of Ag-loaded B-doped gC3N4 NS. Combined effect of all three strategies successfully produced over 5 times higher rate towards degradation of organic dye pollutant, when compared to unmodified bulk gC3N4. Detailed characterization results revealed that incorporation of B in gC3N4 matrix reduces the band gap to increase the visible light absorption, while specific surface area is significantly enhanced upon formation of NS. Decoration of Ag nanoparticles (NPs) on B-doped gC3N4 NS assists in fast transfer of photogenerated electrons from gC3N4 to Ag NPs owing to the interfacial electric field across the junctions and thus reduces the recombination process. Investigations on individual strategies revealed that decoration of Ag NPs to induce better charge separation, is the most effective route for enhancing the photocatalytic activity.

Purpose: The ability of natural killer (NK) cells to lyse allogeneic targets, without the need for explicit matching or priming, makes them an attractive platform for cell-based immunotherapy. Umbilical cord blood is a practical source for generating banks of such third-party NK cells for “off-the-shelf” cell therapy applications. NK cells are highly cytolytic, and their potent antitumor effects can be rapidly triggered by a lack of HLA expression on interacting target cells, as is the case for a majority of solid tumors, including neuroblastoma. Neuroblastoma is a leading cause of pediatric cancer–related deaths and an ideal candidate for NK-cell therapy. However, the antitumor efficacy of NK cells is limited by immunosuppressive cytokines in the tumor microenvironment, such as TGFβ, which impair NK cell function and survival. Experimental Design: To overcome this, we genetically modified NK cells to express variant TGFβ receptors, which couple a mutant TGFβ dominant-negative receptor to NK-specific activating domains. We hypothesized that with these engineered receptors, inhibitory TGFβ signals are effectively converted to activating signals. Results: Modified NK cells exhibited higher cytotoxic activity against neuroblastoma in a TGFβ-rich environment in vitro and superior progression-free survival in vivo, as compared with their unmodified controls. Conclusions: Our results support the development of “off-the-shelf” gene-modified NK cells, that overcome TGFβ-mediated immune evasion, in patients with neuroblastoma and other TGFβ-secreting malignancies.

Reduced graphene oxide (rGO) TiO2 composites are prepared using photo-reduction method by varying GO to TiO2 weight ratio from low (rGOT-0.001, 0.01, & 0.1) to high (rGOT-1, 3 & 10) range and its effect on morphological, optical and mechanism of fast charge dynamics at the interface are investigated. Experimental analysis confirm that reduction process improves as TiO2 amount increases in rGO-TiO2 but leads to aggregation of TiO2 nanoparticles. rGOT-3 composite displayed the highest photocatalytic activity for degradation of phenols compared to TiO2, GO and other composites. This was achieved due to uniform dispersion of TiO2 nanoparticles over rGO surface, which enables distinct formation of Ti O C bond between each TiO2 nanoparticle and rGO surface, and results in slight red shift in the band edge. This Ti O C bond facilitates fast electron transfer from TiO2 to rGO and reduces recombination rate as revealed by photoluminescence and time resolved photoluminescence spectroscopy. The experimental findings were further investigated using density functional theory simulations. Band structure calculation confirms high mobility states induced within the band gap due to formation of Ti O C bond in rGO-TiO2 model which assists in fast electron transfer from TiO2 to rGO during the photocatalytic process and hence reduces recombination rate.

Immune checkpoint blockade (ICB) comprising monoclonal antibodies (mAbs) against immune ‘checkpoints’, such as CTLA-4 and the PD1/PDL1 axis have dramatically improved clinical outcomes for patients with cancer. However, ICB by itself has failed to provide benefit in a wide range of solid tumors, where recurrence still occurs with high incidence. These poor response rates may be due to the therapeutic shortcomings of ICB; namely, a lack of cancer-specific cytotoxicity and ability to debulk tumors. To overcome these limitations, effective ICB therapy may require the combination with other complementary therapeutic platforms. Here, we propose that photothermal therapy (PTT) is an ideal therapeutic modality for combination with ICB because it can generate both tumor-specific cytotoxicity and immunogenicity. PTT elicits these specific effects because it is a localized thermal ablation technique that utilizes light-responsive nanoparticles activated by a wavelength-matched laser. While ICB immunotherapy alone improves cancer immunogenicity but does not generate robust antitumor cytotoxicity, nanoparticle-based PTT elicits targeted and controlled cytotoxicity but sub-optimal long-term immunogenicity. Thus, the two platforms offer complementary and potentially synergistic antitumor effects, which will be detailed in this review. We highlight three classes of nanoparticles used as agents of PTT (i.e., metallic inorganic nanoparticles, carbon-based nanoparticles and organic dyes), and illustrate the potential for nanoparticle-based PTT to potentiate the effects of ICB in preclinical models. Through this discussion, we aim to present PTT combined with ICB as a potent synergistic combination treatment for diverse cancer types currently refractory to ICB as well as PTT monotherapies.

Despite the outstanding clinical results of immune checkpoint blockade (ICB) in melanoma and other cancers, clinical trials in breast cancer have reported low responses to these therapies. Current efforts are now focused on improving the treatment efficacy of ICB in breast cancer using new combination designs such as molecularly targeted agents, including histone deacetylase inhibitors (HDACi). These epigenetic drugs have been widely described as potent cytotoxic agents for cancer cells. In this work, we report new noncanonical regulatory properties of ultra-selective HDAC6i over the expression and function of epithelial–mesenchymal transition pathways and the invasiveness potential of breast cancer. These unexplored roles position HDAC6i as attractive options to potentiate ongoing immunotherapeutic approaches. These new functional activities of HDAC6i involved regulation of the E-cadherin/STAT3 axis. Pretreatment of tumors with HDAC6i induced critical changes in the tumor microenvironment, resulting in improved effectiveness of ICB and preventing dissemination of cancer cells to secondary niches. Our results demonstrate for the first time that HDAC6i can both improve ICB antitumor immune responses and diminish the invasiveness of breast cancer with minimal cytotoxic effects, thus departing from the cytotoxicity-centric paradigm previously assigned to HDACi.Significance:Ultraselective HDAC6 inhibitors can reduce tumor growth and invasiveness of breast cancer by noncanonical mechanisms unrelated to the previously cytotoxic properties attributed to HDAC inhibitors.

We report the generation of magnetically responsive, cord blood-derived natural killer (NK) cells using iron oxide nanoparticles (IONPs). NK cells are a promising immune cell population for cancer cell therapy as they can target and lyse target tumor cells without prior education. However, NK cells cannot home to disease sites based on antigen recognition, instead relying primarily on external stimuli and chemotactic gradients for transport. Hence, we hypothesized that conjugating IONPs onto the surface of NK cells provides an added feature of magnetic homing to the NK cells, improving their therapeutic function. We describe a robust design for conjugating the IONPs onto the surface of NK cells, which maintains their intrinsic phenotype and function. The conferred magnetic-responsiveness is utilized to improve the cytolytic function of the NK cells for target cells in 2D and 3D models. These findings demonstrate the feasibility of improving NK cell homing and therapeutic efficacy with our NK:IONP "biohybrid".

We describe the synthesis of CpG oligodeoxynucleotide-coated Prussian blue nanoparticles (CpG-PBNPs) that function as a nanoimmunotherapy for neuroblastoma, a common childhood cancer. These CpG-PBNPs increase the antigenicity and adjuvanticity of the treated tumors, ultimately driving robust antitumor immunity through a multi-pronged mechanism. CpG-PBNPs are synthesized using a facile layer-by-layer coating scheme resulting in nanoparticles that exhibit monodisperse size distributions and multiday stability without cytotoxicity. The strong intrinsic absorption of PBNPs in the CpG-PBNPs enables ablative photothermal therapy (CpG-PBNP-PTT) that triggers tumor cell death, as well as the release of tumor antigens to increase antigenicity. Simultaneously, the CpG coating functions as an exogenous molecular adjuvant that complements the endogenous adjuvants released by the CpG-PBNP-PTT (e.g. ATP, calreticulin, and HMGB1). In cell culture, coating NPs with CpG increases immunogenicity while maintaining the photothermal activity of PBNPs. When administered in a syngeneic, Neuro2a-based, murine model of neuroblastoma, CpG-PBNP-PTT results in complete tumor regression in a significantly higher proportion (70% at 60 days) of treated animals relative to controls. Furthermore, the long-term surviving, CpG-PBNP-PTT-treated animals reject Neuro2a rechallenge, suggesting that this therapy generates immunological memory. Our findings point to the importance of simultaneous cytotoxicity, antigenicity, and adjuvanticity to generate robust and persistent antitumor immune responses against neuroblastoma.

High-risk neuroblastoma, which is associated with regional and systemic metastasis, is a leading cause of cancer-related mortality in children. Responding to this need for novel therapies for high-risk patients, we have developed a "nanoimmunotherapy," which combines photothermal therapy (PTT) using CpG oligodeoxynucleotide-coated Prussian blue nanoparticles (CpG-PBNPs) combined with anti-CTLA-4 (aCTLA-4) immunotherapy. Our in vitro studies demonstrate that in addition to causing ablative tumor cell death, our nanoimmunotherapy alters the surface levels of co-stimulatory, antigen-presenting, and co-inhibitory molecules on neuroblastoma tumor cells. When administered in a syngeneic, murine model of neuroblastoma bearing synchronous Neuro2a tumors, the CpG-PBNP-PTT plus aCTLA-4 nanoimmunotherapy elicits complete tumor regression in both primary (CpG-PBNP-PTT-treated) and secondary tumors, and long-term survival in a significantly higher proportion (55.5%) of treated-mice compared with the controls. Furthermore, the surviving, nanoimmunotherapy-treated animals reject Neuro2a rechallenge, suggesting that the therapy generates immunological memory. Additionally, the depletion of CD4+, CD8+, and NK+ populations abrogate the observed therapeutic responses of the nanoimmunotherapy. These findings demonstrate the importance of concurrent PTT-based cytotoxicity and the antitumor immune effects of PTT, CpG, and aCTLA-4 in generating a robust abscopal effect against neuroblastoma.

In this contribution we report on an in-depth electrochemical impedance spectroscopy (EIS) study of the interfaces and processes involved in the photoelectrochemical hydrogen production by efficient p-type silicon (pSi) photocathodes, designedly functionalized with protective and catalytic layers. In particular, we have optimized the thermal evaporation of compact and conformal ultra-thin (5 nm) Ti films on pSi, with the double aim of (i) protecting the pSi surface from passivation and photocorrosion, as well as of (ii) introducing platforms with improved adhesion properties for the further functionalization with co-catalysts (in the specific, Pt nanoparticles). The best performing electrodes (labelled as pSi-5Ti-Pt) display an improved photocurrent onset ( ca. 200 mV positive shift in 1 M H 2 SO 4 ), as well as a more than doubled saturation photocurrent (up to −27 mA/cm 2 ) when compared to the unmodified pSi photocathodes. As evidenced by the EIS analysis, the proposed modifications of pSi surface led to an enhancement of the charge extraction from the semiconductor, most likely due to surface dipole effects able to reduce the resistance associated to the transport through the space charge layer. With respect to unmodified silicon, the presence of the Ti overlayer, partially oxidized to TiO 2 , also allows for a denser surface coverage of the electrodeposited Pt nanoclusters, resulting in decreased interfacial charge transfer resistance for hydrogen evolution. The proposed functionalization strategy relies on common fabrication methods (already applied at industrial level) and can be easily extended to other photoelectrode materials prone to passivation/photocorrosion and/or difficult to functionalize, thus introducing more flexibility in the choice of materials for photoelectrochemical cells.

Recombination of photogenerated charges is the main factor affecting the photocatalytic activity of TiO 2 . Here, we report a combined strategy of suppressing both the bulk as well as the surface recombination processes by doping TiO 2 with tungsten and forming a nanocomposite with reduced graphene oxide (rGO), respectively. Sol-gel method was used to dope and optimize the concentration of W in TiO 2 powder. UV-Vis, XPS, PL and time resolved PL spectra along with DFT calculations indicate that W 6+ in TiO 2 lattice creates an impurity level just below the conduction band of TiO 2 to act as a trapping site of electrons, which causes to improve the lifetime of the photo-generated charges. Maximum reduction in the PL intensity and the improvement in charge carrier lifetime was observed for TiO 2 doped with 1 at.% W (1W-TiO 2 ), which also displayed the highest photo-activity for the degradation of p-nitro phenol pollutant in water. Tuning of rGO/TiO 2 ratio (weight) disclosed that the highest activity can be achieved with the composite formed by taking equal amounts of TiO 2 and rGO (1:1), in which the strong interaction between TiO 2 and rGO causes an effective charge transfer via bonds formed near the interface as indicated by XPS. Both these optimized concentrations were utilized to form the composite rGO/1W-TiO 2 , which showed the highest activity in photo-degradation of p-nitro phenol (87%) as compared to rGO/TiO 2 (42%), 1W-TiO 2 (62%) and pure TiO 2 (29%) in 180 min. XPS and PL results revealed that in the present nanocomposite, tungsten species traps the excited electron to reduce the interband recombination in the bulk, while the interaction between TiO 2 and rGO creates a channel for fast transfer of excited electrons towards the latter before being recombined on the surface defect sites.

3D hierarchical nanostructured hematite (α-Fe2O3) coatings containing various shapes were developed by pulsed laser deposition (PLD). A cold pressed, homogeneous mixture of Fe and H3BO3 (Fe + H3BO3) was used as a target in PLD to deposit the coatings in O2 atmosphere. Phase explosion phenomenon provided by laser ablation on the target, allowed to form rough, porous and embedded metallic Fe particulates coating with H3BO3 as background on a glass substrate. Subsequent thermal annealing of the as deposited Fe + H3BO3 coating at 600 °C, led to formation of crystalline, hierarchical 3D nanostructured features with nanowires, nanorods, and nanosheets grown from the spherical particulates. Characterization by XRD, Micro-Raman, XPS, SEM and KPM analysis provided information on the systematic phase and morphology transformation from metallic Fe to hierarchical Iron oxide. Stress-induced phase segregation and stress release process during thermal annealing are suggested as the growth mechanism for the nanostructures. Photocatalytic activity measurements were studied with the coating in presence of Methylene Blue dye through Photo-Fenton process. To understand the effect of precursors, morphology, and synthesis technique (physical and chemical), similar hematite nanostructures were also prepared by thermal annealing of as deposited metallic Fe coating, hematite nanoparticles assembled coating by PLD, and by hydrothermal chemical method respectively. All these coatings showed less photocatalytic activity as compared to the hematite coating obtained from thermal annealing of Fe + H3BO3 sample. A series of various parameters such as effect of H2O2 concentration, effect of pH, water medium and recyclability tests for 10 times were performed, and all revealed promising results in terms of enhanced activity and high mechanical stability of the coatings. Presence of various 3D hierarchical nanostructures, high aspect ratio, more exposed active sites, increased interactions between catalyst surface and reactant dye molecules, and enhanced charge carrier separation, with immobilized stable coating form developed by PLD contributed to achieve the enhanced and stable photocatalytic activity.

Theranostic nanoparticles offer the potential for mixing and matching disparate diagnostic and therapeutic functionalities within a single nanoparticle for the personalized treatment of diseases. In this article, we present composite iron oxide-gadolinium-containing Prussian blue nanoparticles (Fe3O4@GdPB) as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI) and photothermal therapy (PTT) of tumors. These particles combine the well-described properties and safety profiles of the constituent Fe3O4 nanoparticles and gadolinium-containing Prussian blue nanoparticles. The Fe3O4@GdPB nanoparticles function both as effective MRI contrast agents and PTT agents as determined by characterizing studies performed in vitro and retain their properties in the presence of cells. Importantly, the Fe3O4@GdPB nanoparticles function as effective MRI contrast agents in vivo by increasing signal:noise ratios in T1-weighted scans of tumors and as effective PTT agents in vivo by decreasing tumor growth rates and increasing survival in an animal model of neuroblastoma. These findings demonstrate the potential of the Fe3O4@GdPB nanoparticles to function as effective theranostic agents.

We have employed template-free synthesis of CuCo2O4 (CCO) system to achieve unique ultrathin porous nanowall type morphology, and evaluated for Li-Ion battery anode application. We observe that under the hydrothermal growth a starting stoichiometric mixture of cationic precursor’s leads to a bi-phasic constitution comprising of defect-spinel CCO and a small quantity of CuO. Use of the excess but optimum cobalt in the precursor mix leads to single phase defect-spinel. We have carefully examined the implications of off-stoichiometry for different cases of interest (including the case of Cu-excess) for morphology, microstructure, the physical/electrochemical properties, and the evolution of the Li-ion battery anode under cycling for different active materials loading. In case of optimum Cu excess based CCO renders an impressive performance as Li-ion battery anode with high rate performance, 836 mAh g−1 and 757 mAh g−1 at 1.25C and 2.5C, respectively, and good cycling stability.

Silver-polypyrrole nanocomposite (Ag-Ppy) films with different silver concentrations were synthesized without using any external oxidant i.e., with in-situ oxidation of pyrrole in the presence of silver nanoparticles. The gas sensing performance of all the films were investigated for NO, NO 2 , NH 3 , H 2 S , ethanol and methanol gases/vapours. The nanocomposite film was further doped with 05–25% p -toluenesulfonic acid (pTSA). Among various compositions, 15% pTSA doped Ag-Ppy thin films were found to be most sensitive and selective towards NO 2 gas at room temperatures. The films exhibited a chemiresitive response of 68% at 100 ppm NO 2 with a response time of 148 s and a recovery time of 500 s. The films exhibited 21% response for NO 2 even at low concentration levels at 5 ppm. The improved response kinematics is attributed to porous structure with faster charge transfer through ohmic contacts between polymer and silver nanoparticles upon interaction with gas.

In this study, we describe poly (lactic-co-glycolic) acid (PLGA)-based nanoparticles that combine photothermal therapy (PTT) with epigenetic therapy for melanoma. Specifically, we co-encapsulated indocyanine green (ICG), a PTT agent, and Nexturastat A (NextA), an epigenetic drug within PLGA nanoparticles (ICG-NextA-PLGA, INAPs). We hypothesized that combining PTT with epigenetic therapy elicits favorable cytotoxic and immunomodulatory responses that result in improved survival in melanoma-bearing mice. We utilized a nanoemulsion synthesis scheme to co-encapsulate ICG and NextA within stable and monodispersed INAPs. The INAPs exhibited concentration-dependent and near-infrared (NIR) laser power-dependent photothermal heating characteristics, and functioned as effective single-use agents for PTT of melanoma cells in vitro. The INAPs functioned as effective epigenetic therapy agents by inhibiting the expression of pan-histone deacetylase (HDAC) and HDAC6-specific activity in melanoma cells in vitro. When used for both PTT and epigenetic therapy in vitro, the INAPs increased the expression of co-stimulatory molecules and major histocompatibility complex (MHC) Class I in melanoma cells relative to controls. These advantages persisted in vivo in a syngeneic murine model of melanoma, where the combination therapy slowed tumor progression and improved median survival. These findings demonstrate the potential of INAPs as agents of PTT and epigenetic therapy for melanoma.

The photocatalytic performance of gC3N4 is majorly restricted by insufficient collection of photogenerated charges on the surface during reaction due to highly dense stacking of lamellar structures with lateral size ranging in microns. This deficiency can be overcome by forming thin nanoflakes by systematically breaking the weak bonds that hold the gC3N4 framework without destroying the basic heptazine unit. With this aim, herein, a combination of three different strategies was implemented to design and develop, Ag-loaded and P-doped gC3N4 nanoflakes (Ag3-P1-NF-gC3N4). Using a systematic synthesis method, bulk gC3N4 was first converted into thin nanosheets, followed by fragmentation into nanoflakes, with a planar size up to 100 nm. P doping to replace the corner C atoms in the gC3N4 matrix (forming P N bonds) and intercalation of plasmonic Ag nanoparticles within the interlayers also assists in the bifurcation of the stacked layers and formation of nanoflake morphology. These strategies result in a significant increase in BET surface area to ∼196 m2/g from 12 m2/g of bulk gC3N4. Improved inter-planar and intra-planar charge mobility was recorded as a result of the reduced sizes. Doping with P also causes higher absorption of the visible spectrum in gC3N4 while the formation of heterojunction with Ag nanoparticles induces efficient separation of photo-generated charges. All these promoting photo-physical properties lead to an outstanding photocatalytic activity towards degradation of aqueous pollutants with reaction rates ∼20 times higher than bulk gC3N4. Complete mineralization of the pollutant and formation of non-toxic byproducts was also confirmed with suitable chromatography techniques.