Hybrid Nanosystem Research Articles

Thermosensitive Hydrogel-Functionalized Mesoporous Silica Nanoparticles for Parenteral Application of Chemotherapeutics.

Hydrogels can offer many opportunities for drug delivery strategies. They can be used on their own, or their benefits can be further exploited in combination with other nanocarriers. Intelligent hydrogels that react to changes in the surrounding environment can be utilized as gatekeepers and provide sustained on-demand drug release. In this study, a hybrid nanosystem for temperature- and pH-sensitive delivery was prepared from MCM-41 nanoparticles grafted with a newly synthesized thermosensitive hydrogel (MCM-41/AA-g-PnVCL). The initial particles were chemically modified by the attachment of carboxyl groups. Later, they were grafted with agar (AA) and vinylcaprolactam (VCL) by free radical polymerization. Doxorubicin was applied as a model hydrophilic chemotherapeutic drug. The successful formulation was confirmed by FT-IR and TGA. Transmission electron microscopy and dynamic light scattering analysis showed small particles with negative zeta potential. Their release behaviour was investigated in vitro in media with different pH and at different temperatures. Under tumour simulating conditions (40 °C and pH 4.0), doxorubicin was almost completely released within 72 h. The biocompatibility of the proposed nanoparticles was demonstrated by in vitro haemolysis assay. These results suggest the possible parenteral application of the newly prepared hydrogel-functionalized mesoporous silica nanoparticles for temperature-sensitive and pH-triggered drug delivery at the tumour site.

Single photon routing based on the selective coupling of the side-branch in the Plasmonic hybrid nanosystem with dipole–dipole interaction

We propose a theoretical model for the single photon quantum router that consists of two plasmonic waveguides, one of which is infinite and the other is semi-infinite, coupled to two two-level quantum dots (QDs) with dipole–dipole interaction (DDI). The infinite waveguide, the main branch, couples with both QDs, and the semi-infinite, the side branch, couples with the main branch at the position of one of the QDs. In such a system the incident single photon can also be transferred to the side branch, not only be transmitted or reflected. The results show that the transfer rate mainly depends on the coupling strength between the QDs and the two waveguides, but there exists a certain limit in the increase of the transfer rate. The DDI between the QDs gives a remarkable change to the routing spectra and the routing properties are different according to the position of the side branch. The proposed system is indeed multi-channel single photon quantum router, which has more practical significance than the one-dimensional router and can be employed in multi-user quantum networking.

Enhanced second harmonic generation from a hybrid nanosystem consisting of a semiconductor quantum dot in the presence of two spheroidal plasmonic nanoparticles

Enhanced second harmonic generation from a hybrid nanosystem consisting of a semiconductor quantum dot in the presence of two spheroidal plasmonic nanoparticles

Reversing immune evasion using a DNA nano-orchestrator for pancreatic cancer immunotherapy.

Immune evasion caused by the paucity of MHCI is a prominent characteristic of pancreatic adenocarcinoma (PAAD), which is thought to underlie dysfunctional even absent adaptive T cell immunity and is responsible for ineffective immunotherapy. Here, we report a ROS-responsive DNA nano-orchestrator to cascade reverse MHC I-associated immune evasion and boost anti-tumor T cell stimulation, stimulating the activation of tumoricidal immunity against PAAD. Chloroquine phosphate (CQP) as an autophagy inhibitor was first encapsulated with ferritin, and via DNA modular self-assembly technology, the generated ferritin nanocores (FNC) were then caged into ROS-responsive CpG-DNA nanoframe. After systemic injection, the FNC-laden DNA nanoframe (FNC@NF) was passively enriched in tumor tissues in which the DNA nanoframe was cleaved upon the ROS stimulation. Oligodeoxynucleotide (ODN) with CpG motifs was detached and functioned as a TLR9 agonist. The liberated FNC was then endocytosed in an actively targeted manner by binding to transferrin receptor 1. In the lysosome, CQP was burst released from FNC due to acid-triggering. Through CQP-mediated autophagy abrogation, MHC-I molecules were preserved. We demonstrated that cascade inhibiting autophagy and boosting TLR9 stimulation via our proposed DNA-based hybrid nanosystem restored MHC I on the tumor cell surface and reshaped the antigen presentation of DCs, and ultimately reversed immune evasion and synergistically reinforced the activation of cytotoxic T cells against PAAD cells. In sum, our work provides an alternative strategy for cascade reversing immune evasion and boosting anti-tumor T cell stimulation and holds great potential for pancreatic cancer immunotherapy. STATEMENT OF SIGNIFICANCE: A DNA nano-orchestrator was created by sequentially assembling chloroquine phosphate-laden ferritin nanocores with ROS-responsive CpG-DNA nanoframe. Through cascade inhibiting autophagy and boosting TLR9 stimulation, the nano-orchestrator efficiently reversed MHC I-associated immune evasion and augmented anti-tumor T cell stimulation, which ultimately activated tumoricidal immunity against pancreatic adenocarcinoma.

Self-assembled Gallic acid loaded lecithin-chitosan hybrid nanostructured gel as a potential tool against imiquimod-induced psoriasis

Increased thickness of the skin and hyperproliferation of keratinocyte cell is the main obstacle in the treatment of psoriasis. Gallic Acid (GA) has shown efficacious results against the hyperproliferation of keratinocytes while lipid-polymer loaded hybrid nanoparticles (LPHNs) have an edge over lipidic and polymeric nanoparticles considering drug loading, controlled release, stability, and retention. The LPHNs were optimized using Box-Behnken method and was further characterized by FTIR, DSC and Zetasizer. The optimized preparation demonstrated a size of 170.5 ± 0.087 nm and a PDI of 0.19 ± 0.0015, respectively. The confocal study has suggested that the hybrid nanosystem enhanced the drug penetration into the deeper layer with a higher drug release of 79 ± 0.001% as compared to the gallic acid-loaded gel. In addition, the formulation significantly reduced PASI score and splenomegaly without causing any serious irritation. The morphological study of the spleen suggested that the prepared formulation has well controlled the disease compared to the marketed formulation while maintaining a normal level of immune cells after treatment. Hence GALPHN could be accepted as one of the excellent vehicles for the topical conveyance of GA (gallic acid) due to enhanced penetration, and good retention, along with fewer side effects and higher efficacy of the GALPHN gel against imiquimod (IMQ) induced psoriasis.

Thermoresponsive M1 macrophage-derived hybrid nanovesicles for improved in vivo tumor targeting

Despite the efforts and advances done in the last few decades, cancer still remains one of the main leading causes of death worldwide. Nanomedicine and in particular extracellular vesicles are one of the most potent tools to improve the effectiveness of anticancer therapies. In these attempts, the aim of this work is to realize a hybrid nanosystem through the fusion between the M1 macrophages-derived extracellular vesicles (EVs-M1) and thermoresponsive liposomes, in order to obtain a drug delivery system able to exploit the intrinsic tumor targeting capability of immune cells reflected on EVs and thermoresponsiveness of synthetic nanovesicles. The obtained nanocarrier has been physicochemically characterized, and the hybridization process has been validated by cytofluorimetric analysis, while the thermoresponsiveness was in vitro confirmed through the use of a fluorescent probe. Tumor targeting features of hybrid nanovesicles were in vivo investigated on melanoma-induced mice model monitoring the accumulation in tumor site through live imaging and confirmed by cytofluorimetric analysis, showing higher targeting properties of hybrid nanosystem compared to both liposomes and native EVs. These promising results confirmed the ability of this nanosystem to combine the advantages of both nanotechnologies, also highlighting their potential use as effective and safe personalized anticancer nanomedicine.Graphical

Qualitative assessment on cisplatin loaded CeO2/Au/GO hybrid as theranostics platform in HeLa cell lines

Nanomaterials have been increasingly popular in bioimaging and cancer therapy due to their unique characteristics to reachtarget-specific tumours. Due to this uniqueness, a drug delivery platform made of nanomaterials has been developed to deliver theanti-cancer drug to target sites. As the number of incidences of cancer increases, it is critical to provide a medication delivery platform for treating cancer as soon as possible. Also, nanosystems based on carbon have been widely used as a possible biomarker for cancer imaging and therapeutics. This research work primarily focuses on the development of a spherical-shaped porous CeO2/Au/GO hybrid nanocomposite to serve as a nanoplatform to treatcervical cancer. The stacked layer of graphene oxide (GO) was loaded with porous aminated cerium oxide nanoparticles (CeO2 NPs) and gold nanoparticles (Au NPs). X-ray Diffraction (XRD),Field Emission Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) were used to investigate their physio-chemical properties and morphology. Furthermore, HeLa cells were interacted with the suggested porous Au/GO hybrid, CeO2/Au/GO hybrid nanosystem and cisplatin-loaded CeO2/Au/GO hybrid system (CeO2/Cis-Au/GO hybrid), under in-vitro conditions to assess the anti-cancer efficacy of the proposed nanoplatforms. In this study, the minimum concentration of Au/GO at which nearly 50% of the cells remain dead (IC50 concentration)is considered to be 62.5 µg/mL and 31.2 µg/mL for CeO2/Au/GO. Further, the cisplatin anticancer drug was chemically bonded with CeO2/Au/GO hybrid nanosystem for testing the apoptotic efficacy of cancer cells under in-vitro conditions. The IC50 value was 62.5 µg/mL which affirmed the anticancer property of the CeO2/Cis-Au/GO system with HeLa cells. According to the findings from the antiproliferative assay, CeO2/Au/GO nanoplatforms resulted in superior cytotoxicity effects on cervical cancer in comparison with CeO2/Cis-Au/GO and Au/GO nanoplatform. Lastly, the proposed CeO2/Au/GO hybrid nanosystem was subject to dual staining investigation using Acridine Orange/Ethidium Bromide (AO/EB) dyes for recording the morphological changes incurred and also to visualize live and dead cells using fluorescence spectroscopy. Based on these findings, the developed CeO2/Au/GO hybrid nanosystem can be taken to in vivo studies for the validation to act as a theranostic platform for cervical cancer.

Laser shock introduces strained wrinkling of CVD monolayer MoS2 and atomic gapping of plasmonic phototransistors

Monolayer MoS2, an atomic direct bandgap 2D material with excellent mechanical properties, is considered one of the top candidates for next-generation electronics. However, the phototransistor based on MoS2 synthesized through chemical vapor deposition (CVD) has relatively weak optical emissivity and absorption, low field-effect mobility, and a narrow response spectral range These limitations hinder the widespread application of MoS2 in optoelectronic devices. Here, to improve the performance of CVD 2D electronic devices in large-scale applications, we designed a hybrid nano-system with laser shock-enhanced plasmon and strain coupling. Wrinkles of CVD monolayers of MoS2 sandwiched between two layers of Ag nanoparticles (NPs) are tensile strained to form gap-mode localized surface plasmon resonance (LSPR). The strain of the laser shock (LS) leads to the co-deformation of MoS2 and Ag NPs, achieving an extremely narrow gap LSPR (<1 nm). The residual inhomogeneous elastic strain, remaining after the shock, not only enhances the LSPR but also modulates the band structure of MoS2 favorably. In comparison to a phototransistor employing CVD-monolayer MoS2 on a flat substrate (1L-MoS2), the laser-shock phototransistor (LS_Ag-MoS2) is improved by nearly 50 times, the response range is extended to near-infrared, and the field effect mobility is increased by 30 times. In addition, the response time is reduced from 1.28 s to 20 ms, which is comparable to the current high-K dielectric multilayer MoS2 phototransistor. Our work presents an advanced and scalable fabrication method for future applications of ultra-thin and high-performance phototransistors utilizing CVD two-dimensional materials.

Biocompatible polysaccharide fabricated graphene oxide nanoparticles: A versatile nanodrug carrier to deliver κ- carrageenan against cancer cells

A graphene oxide mediated hybrid nano system for pH stimuli-responsive and in vitro drug delivery targeted for cancer was described in this study. Graphene oxide (GO) functionalized Chitosan (CS) mediated nanocarrier capped with xyloglucan (XG) was fabricated with and without Kappa carrageenan (κ-C) from red seaweed, Kappaphycus alverzii, as an active drug. FTIR, EDAX, XPS, XRD, SEM and HR-TEM studies were carried out for GO-CS-XG nanocarrier loaded with and without active drugs to understand the physicochemical properties. XPS (C1s, N1s and O1s) confirmed the fabrications of XG and functionalization of GO by CS via the binding energies at 284.2 eV, 399.4 eV and 531.3 eV, respectively. The amount of drug loaded in vitro was 0.422 mg/mL. The GO-CS-XG nanocarrier showed a cumulative drug release of 77 % at acidic pH 5.3. In contrast to physiological conditions, the release rate of κ-C from the GO-CS-XG nanocarrier was considerably higher in the acidic condition. Thus, a pH stimuli-responsive anticancer drug release was successfully achieved with the GO-CS-XG-κ-C nanocarrier system for the first time. The drug release mechanism was carried out using various kinetic models that showed a mixed release behavior depending on concentration and diffusion/swelling mechanism. The best-fitting model which supports our release mechanism are zero order, first order and Higuchi models. GO-CS-XG and κ-C loaded nanocarrier biocompatibility were determined by in vitro hemolysis and membrane stabilization studies. MCF-7 and U937 cancer cell lines were used to study the cytotoxicity of the nanocarrier by MTT assay, which indicates excellent cytocompatibility. These findings support the versatile use of a green renewable biocompatible GO-CS-XG nanocarrier as targeted drug delivery and potential anticancer agent for therapeutic purposes.

Synthesis and Exploring the Structural, Electrical and Optical Characteristics of PVA/TiN/SiO2 Hybrid Nanosystem for Photonics and Electronics Nanodevices

Synthesis and Exploring the Structural, Electrical and Optical Characteristics of PVA/TiN/SiO2 Hybrid Nanosystem for Photonics and Electronics Nanodevices

Fabrication and Augmented Structural, Optical and Electrical Features of PVA/Fe2O3/SiC Hybrid Nanosystem for Optics and Nanoelectronics Fields

Fabrication and Augmented Structural, Optical and Electrical Features of PVA/Fe2O3/SiC Hybrid Nanosystem for Optics and Nanoelectronics Fields

Phase-transition nanodroplets with immunomodulatory capabilities for potentiating mild magnetic hyperthermia to inhibit tumour proliferation and metastasis

BackgroundMagnetic hyperthermia (MHT)-mediated thermal ablation therapy has promising clinical applications in destroying primary tumours. However, traditional MHT still presents the challenges of damage to normal tissues adjacent to the treatment site and the destruction of tumour-associated antigens due to its high onset temperature (> 50 °C). In addition, local thermal ablation of tumours often exhibits limited therapeutic inhibition of tumour metastasis.ResultsTo address the above defects, a hybrid nanosystem (SPIOs + RPPs) was constructed in which phase transition nanodroplets with immunomodulatory capabilities were used to potentiate supermagnetic iron oxide nanoparticle (SPIO)-mediated mild MHT (< 44 °C) and further inhibit tumour proliferation and metastasis. Magnetic-thermal sensitive phase-transition nanodroplets (RPPs) were fabricated from the immune adjuvant resiquimod (R848) and the phase transition agent perfluoropentane (PFP) encapsulated in a PLGA shell. Because of the cavitation effect of microbubbles produced by RPPs, the temperature threshold of MHT could be lowered from 50℃ to approximately 44℃ with a comparable effect, enhancing the release and exposure of damage-associated molecular patterns (DAMPs). The exposure of calreticulin (CRT) on the cell membrane increased by 72.39%, and the released high-mobility group B1 (HMGB1) increased by 45.84% in vivo. Moreover, the maturation rate of dendritic cells (DCs) increased from 4.17 to 61.33%, and the infiltration of cytotoxic T lymphocytes (CTLs) increased from 10.44 to 35.68%. Under the dual action of mild MHT and immune stimulation, contralateral and lung metastasis could be significantly inhibited after treatment with the hybrid nanosystem.ConclusionOur work provides a novel strategy for enhanced mild magnetic hyperthermia immunotherapy and ultrasound imaging with great clinical translation potential.

Abstract 832: Exosome-based hybrid nanosystem for targeted TNBC therapy

Abstract Treatment of metastatic Triple-Negative Breast Cancer (TNBC) remains a challenge despite an increasing number of newer drugs being approved in recent years. The major challenge for improved treatment outcomes for metastatic cancer originates from the fact that the drugs are unable to reach the targeted site and hence are not able to elicit the desired response. Recently, natural mesenchymal stem cells (MSC) cells and their exosomes have been shown to have tumor-homing properties. By exploiting these homing properties, we propose the development of an exosome-polymeric hybrid nanosystem (EPHN) by using exosomes for their targeting ability to enhance the targetability and thus the therapeutic efficacy of the drug against TNBC. In this study, we bioengineered MSC exosome-coated drug-loaded polymeric nanoparticles to deliver our chemotherapeutic drug in a targeted fashion. To isolate the MSC exosomes, we grew the cells in exosome-free media and used the ultracentrifugation standard method. The MSC exosomes had a size of approximately 70 ± 5 nm and a PDI of 0.3. Our exosome sample was positive for exosomal proteins and negative for all other extracellular vesicles. The optimal doxorubicin-loaded PLGA nanoparticles were prepared using a microfluidics method resulting in a higher entrapment efficiency of 42 ± 3% and a smaller size of 70 ± 3 nm and a PDI of 0.2. To make the exosome-coated NPs, we used the extrusion method. After extrusion, the zeta potential of our EPHN was closer to -11mV compared to PLGA NPs (-50mV), which demonstrates that our NPs were coated with an exosomal membrane. We were able to make MSC exosome-coated drug-loaded polymeric nanoparticles and show that they were stable and uniform in size. Microfluidics-assisted doxorubicin-loaded PLGA nanoparticles show uniform size and higher entrapment efficiency. Release kinetics showed a strong burst phase release over the first 8 hours and subsequent sustained release up to 72 hours. In vivo biodistribution of EPHN shows better tumor accumulation compared to PLGA NP. The next stage in this project is in vivo tumor efficacy testing in breast cancer tumor models. This targeted NP system can serve as a novel therapeutic platform for developing improved treatments for metastatic TNBC. Citation Format: Rohan Joshi, Jana Lampe, Jamboor K. Vishwanatha, Amalendu P. Ranjan. Exosome-based hybrid nanosystem for targeted TNBC 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 832.

Light excitation of gold Nanorod-Based hybrid nanoplatforms for simultaneous bimodal phototherapy

In this work, we developed a hybrid nanosystem able to simultaneously combine its potential as a photodynamic (PDT) and plasmonic photothermal (PPTT) therapeutic agent to kill malignant cells. To do that, AuNRs were functionalized by means of the layer-by-layer (LbL) assembly technique using alternating layers of anionic poly(styrene sulfonate) (PSS) and cationic poly-L-lysine (PLL) as polyelectrolytes (PEs), and an outer final layer of hyaluronic acid (HA) to provide the hybrid particles with both sufficient colloidal stability and targeting ability to tumoral cells overexpressing CD44 receptors. To provide the nanoplatform with PDT capabilities, the near-infrared (NIR) sensitive photosensitizer (PS) indocyanine green (ICG) was previously grafted to the PLL PE and assembled on the particle surface coating; in this manner, PSS/PLL-ICG/HA-coated AuNRs hybrid particles were obtained. Then, the conditions for optimized reactive oxygen species (ROS) production under NIR light excitation were elucidated, reaching ca. 80% after 5 min irradiation at 2.0 W/cm2 compared to positive control (H2O2). Since ICG can also absorb near infrared (NIR) light and transforms it by internal conversion into heat under suitable irradiation conditions, which adds to the photothermal plasmonic effect provided by the metallic NP, the heating profiles provided by the present hybrid nanoparticles (NPs) were measured, being observed temperature increments ranging from 9 to 22 °C. The potential contribution of its different components to both PDT and PPTT were deeply analyzed in vitro for intended cancer therapeutics at several power intensities but also at different temperatures with the aim of elucidating the role played by both phototherapies on cell cytotoxicity, the optimal illumination conditions for effective bimodal phototherapy as well as the elucidation of the main cell death mechanism involved. Under optimized conditions and after the administration of 2.5 ·1010 NPs/mL, cell cytotoxicites of up to ca. 70% were determined by combination of PDT + PPTT therapeutic effect.

Synthesis of Fe3O4-Gold hybrid nanoparticles coated by bovine serum albumin as a contrast agent in MR imaging

Despite the over spatial separation and the ability to determine soft tissues, insufficient contrast is the shortcoming of magnetic resonance imaging (MRI) that could be circumvented by the use of contrast agents. The use of MRI contrast agents are widely applied to enhance the vision of internal body structures. Nano-sized contrast materials have unique application advantages compared to other contrast agents due to their size and shape. However, for contrast agents such as bare iron (II, III) oxide (Fe3O4) magnetic nanoparticles (NPs), aggregation and accumulation are the main shortcomings. Thus, surface modifications are necessary for their use in biopharmaceutical applications. Gold, Au, nanoparticles are of big interesting for use in biomedical purposes due to their chemical stability and oxidation resistance. In this study, we synthesized magnetic Fe3O4–Au hybrid NPs with a facile method and coated them with bovine serum albumin (BSA) to increase their chemical stability and biocompatibility. Afterwards, the hybrid nanosystem was characterized by some methods, and their potential to increase MRI contrast was investigated by the phantom MRI experiments. Our data showed that the signal intensity on MR images was significantly reduced, thus confirming the contrast ability of the formulated Fe3O4–Au-BSA NPs.

Engineered Hybrid Nanosystem for Homologous Targeting of EMT Induced Triple Negative Breast Cancer Cells.

The increased mortality rate due to metastatic breast cancer with poor prognosis has raised concern over its effective therapy. Though various therapies and anticancer drugs have been approved, there is still a lack in the targeting of metastatic triple negative breast cancer (TNBC). We have developed a hybrid nanosystem that was synthesized by fusing exosomes from MCF-7 cells and nanovesicles from the MDA MB-231 cells that would be targeted. The developed nanosystem was characterized by various techniques like Western blotting, AFM, FETEM, DLS, CD, and fluorescence spectroscopy. The hybrid system was used for the delivery of an HDAC inhibitor, Trichostatin A (TSA), in combination with lapatinib (a tyrosine kinase inhibitor) for cotherapy of epithelial to mesenchymal transition (EMT) induced TNBC. This targeted cotherapy module had higher efficiency and effectivity in the reduction of metastatic ability and proliferation of EMT induced MDA MB-231 cells as compared to free inhibitor treatment or untargeted cotherapy. Reduction in the expression of the Wnt/β-catenin signaling pathway molecules like β-catenin (by 0.7 fold), Gsk3β (by 0.6 fold), and pGsk-3β (0.3 fold) was observed upon treatment. This subsequently resulted in the suppression of EMT markers, thereby resulting in reversing EMT to MET and suppressing metastatic breast cancer.

Rational design of magnetoliposomes for enhanced interaction with bacterial membrane models

There is a growing need for alternatives to target and treat bacterial infection. Thus, the present work aims to develop and optimize the production of PEGylated magnetoliposomes (MLPs@PEG), by encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) within fusogenic liposomes. A Box–Behnken design was applied to modulate size distribution variables, using lipid concentration, SPIONs amount and ultrasonication time as independent variables. As a result of the optimization, it was possible to obtain MLPs@PEG with a mean size of 182 nm, with polydispersity index (PDI) of 0.19, and SPIONs encapsulation efficiency (%EE) around 76%. Cytocompatibility assays showed that no toxicity was observed in fibroblasts, for iron concentrations up to 400μg/ml. Also, for safe lipid and iron concentrations, no hemolytic effect was detected. The fusogenicity of the nanosystems was first evaluated through lipid mixing assays, based on Förster resonance energy transfer (FRET), using liposomal membrane models, mimicking bacterial cytoplasmic membrane and eukaryotic plasma membrane. It was shown that the hybrid nanosystems preferentially interact with the bacterial membrane model. Confocal microscopy and fluorescence lifetime measurements, using giant unilamellar vesicles (GUVs), validated these results. Overall, the developed hybrid nanosystem may represent an efficient drug delivery system with improved targetability for bacterial membrane.

Catalytically proficient ceria nanodots supported on redox-active mesoporous hosts for treatment of inflammatory bowel disease via efficient ROS scavenging.

Ceria nanozyme-based ROS scavengers have shown great potential in the treatment of inflammatory bowel disease (IBD) through microenvironment regulation. However, the currently developed nanotherapeutics suffer from difficulties in concomitantly achieving small sizes and stable interparticle dispersion which is pivotal to sufficient oxygen vacancies facilitating electron transfer and oxygen storage in the dynamic cycling of Ce3+/Ce4+ redox pairs. Herein, a hybrid nanosystem consisting of ceria nanodots supported on redox-active mesoporous hosts was developed to address the challenge of ROS scavenging, in particular the efficient downregulation of the readily renewable, highly concentrated H2O2 species. Specifically, Ce4+ ions oxidized from Ce3+ in weakly basic solution were captured and reduced in time by the abundant catechols on the mesoporous polydopamine nanoparticles. This led to strong restriction of ceria growth (∼2.8 nm) in the ion precipitation process and efficient maintenance of the Ce3+/Ce4+ ratio at a high value of 1.59 which is 4.8 fold higher than that of homogeneously nucleated ceria nanoparticles. Through this design, the nanohybrid showed an attractive catalytic performance in scavenging multiple ROS species, particularly the fast and recyclable conversion of H2O2. Thereby, significant suppression of the inflammatory cytokine/chemokine secretion was achieved by inhibiting the activation of NF-κB signaling pathways (5.1 fold higher as compared to those of pristine ceria nanoparticles), upregulating the Nrf2 signaling pathway, and reducing the proportion of M1 macrophages at IBD sites. Therapeutic efficiency was also demonstrated by the effective repair of the intestinal mucosal barrier by recovering the tight junction integrity in vivo. This study sheds light on the employment of redox-active hosts to support ceria catalysts for advancing anti-inflammation applications by boosting ROS scavenging performance.

Influence of Green Synthesized Zinc Oxide Nanoparticles on Molecular Interaction and Comparative Binding of Azure Dye with Chymotrypsin: Novel Nano-Conjugate for Cancer Phototherapy.

Till date, different types of conventional drugs have been used to fight tumors. However, they have significant flaws, including their usage being constrained because of their low bioavailability, poor supply, and serious side effects. The modern combination therapy has been viewed as a potent strategy for treating serious illnesses, including cancer-type feared diseases. The nanoparticles are a promising choice for cancer therapeutic and diagnostic applications because of their fascinating optoelectronic and physicochemical features. Among the metallic nanoparticles, Zinc oxide nanoparticles possess interesting physicochemical and anti-cancer characteristics, such as ROS generation, high retention, enhanced permeability etc., making them attractive candidates for the treatment and diagnosis of cancer. Zinc oxide nanoparticles showed anti-cancer property via excessive reactive oxygen species (ROS) production, and by the destruction of mitochondrial membrane. Here, we have synthesized organic/inorganic hybrid nanosystem composed of chymotrypsin protein (Chymo) with AzureC (AzC) conjugated with Zinc oxide nanoparticles (ZnONPs). The conjugation of AzureC with ZnONPs was confirmed by transmission electron microscopy (TEM), zeta potential, and dynamic light scattering (DLS) experiment. The interaction of Chymo with AzC alone and AzC-ZnONPs was investigated, and it was observed that the interaction was enhanced in the presence of ZnONPs, which was concluded by the results obtained from different spectroscopic techniques such as UV-Visible spectroscopy, fluorescence spectroscopy and circular dichroism in combination with molecular docking. UV-Visible spectroscopic studies and the corresponding binding parameters showed that the binding of AzC-ZnONPs complex with Chymo is much higher than that of AzC alone. Moreover, the fluorescence measurement showed enhancement in static quenching during titration of Chymo with AzC-ZnONPs as compared to dye alone. In addition to this, circular dichroism results show that the dye and dye-NPs conjugate do not cause much structural change in α-Chymo. The molecular docking and thermodynamic studies showed the predominance of hydrogen bonding, Van der Waal force, and hydrophobic forces during the interactions. After correlation of all the data, interaction of Chymo with AzC-ZnONPs complex showed strong interaction as compared to dye alone. The moderate binding with chymo without any alteration in the structure makes it desirable for the distribution and pharmacokinetics. In addition, the in vitro cytotoxicity of the AzC-ZnONPs was demonstrated on A-549 adenocarcinoma cell line. Our findings from physiochemical investigations suggested that the chymotrypsin coated AzC conjugated ZnONPs could be used as the novel nanoconjugates for various cancer phototherapies.

A sequentially responsive cascade nanoplatform for increasing chemo-chemodynamic therapy

Poly(lactide-co-glycolide) (PLGA) is promising carrier material for drugs delivery in cancer therapy. However, the slow degradation and lack of targeting have greatly limited the clinical effectiveness of PLGA-based nanomedicines. Herein, we fabricated a hybrid nanosystem (3 P @ He/Pt-NPs) comprising of acid-sensitive polymer (mPOE-PLGA), active-targeting polymer (PBA-PLGA) and therapeutic agents (hemin+cisplatin) to combat these problems. In neutral environment, PEGylation can effectively improve the blood stability and circulation time of hybrid nanosystem. After reaching tumor regions, this nanosystem efficiently increased cellular uptake by dePEGylation and PBA-mediated active-targeting. Furthermore, encapsulated hemin could catalyze the oxygen bubbles generation, which remarkably increasing the drugs release rate. Subsequently, hybrid particles produced a higher cell-killing effect to lung cancer cells (A549) by the combination therapy (chemotherapy and chemodynamic therapy (CDT)). Importantly, cisplatin further amplified CDT effect by inducing H2O2 regeneration owing to the cascade enzymatic reactions, while hemin decreased intracellular glutathione (GSH) level, resulting in a low detoxification effect to cisplatin. Thus, hybrid particles could efficiently inhibit drug-resistant tumor growth and the inhibition rate reached 83.2%. Overall, this hybrid polymer nanosystem improve the drawbacks of PLGA-based nanocarriers, and can realize a cascading enhanced tumor treatment.