Search

Intrinsic or acquired resistance to chemical drugs severely limits their therapeutic efficacy in cancer treatment. Various intracellular antioxidant molecules, particularly glutathione (GSH), play a crucial role in maintaining intracellular redox homeostasis by mitigating the overproduced reactive oxygen species (ROS) due to rapid cell proliferation. Notably, these antioxidants also eliminate chemical-drug-induced ROS, eventually diminishing their cytotoxicity and rendering them less effective. In this study, we combined erastin, a GSH biosynthesis inhibitor, with 2'-deoxy-5-fluorouridine 5'-monophosphate sodium salt (FdUMP), an ROS-based drug, to effectively disrupt intracellular redox homeostasis and reverse chemotherapy resistance. Therefore, efficient ferroptosis and apoptosis were simultaneously induced for enhanced antitumor effects. Additionally, we employed small interfering RNA targeting PD-L1 (siPD-L1) as a third agent to block immune-checkpoint recognition by CD8 + T cells. The highly immunogenic cell peroxidates or damage-associated molecular patterns (DAMPs) induced by erastin acted synergistically with downregulated PD-L1 to enhance the antitumor effects. To codeliver these three drugs simultaneously and efficiently, we designed GE11 peptide-modified lipid nanoparticles (LNPs) containing calcium phosphate cores to achieve high encapsulation efficiencies. In vitro studies verified its enhanced cytotoxicity, efficient intracellular ROS induction and GSH/GPX4 downregulation, substantial lipid peroxidation product accumulation, and mitochondrial depolarization. In vivo , this formulation effectively accumulated at tumor sites and achieved significant tumor inhibition in subcutaneous colon cancer (CRC) mouse models with a maximum tumor inhibition rate of 83.89% at a relatively low dose. Overall, a strategy to overcome clinical drug resistance was verified in this study by depleting GSH and activating adaptive immunity.

Aims: Checkpoint blockade immunotherapy is a promising therapeutic modality that has revolutionized cancer treatment; however, the therapy is only effective on a fraction of patients due to the tumor environment. In tumor immunotherapy, the cGAS-STING pathway is a crucial intracellular immune response pathway. Therefore, this study aimed to develop an immunotherapy strategy based on the cGAS-STING pathway., Materials and Methods: The physicochemical properties of the nanoparticles EM@REV@DOX were characterized by TEM, DLS, and WB. Subcutaneous LLC xenograft tumors were used to determine the biodistribution, antitumor efficacy, and immune response. Blood samples and tissues of interest were harvested for hematological analysis and H&E staining., Significance: Overall, our designed nanovesicles provide a new perspective on tumor immunotherapy by ICD and cGAS-STING pathway, promoting DCs maturation, macrophage polarization, and activating T cells, offering a meaningful strategy for accelerating the clinical development of immunotherapy., Key Findings: EM@REV@DOX accumulated in the tumor site through EPR and homing targeting effect to release REV and DOX, resulting in DNA damage and finally activating the cGAS-STING pathway, thereby promoting DCs maturation, macrophage polarization, and activating T cells. Additionally, EM@REV@DOX increased the production of pro-inflammatory cytokines (e.g., TNF-α and IFN-β). As a result, EM@REV@DOX was effective in treating tumor-bearing mice and prolonged their lifespans. When combined with αPD-L1, EM@REV@DOX significantly inhibited distant tumor growth, extended the survival of mice, and prevented long-term postoperative tumor metastasis, exhibiting great potential in antitumor immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

FOLFOX regimen, composed of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (OXP), has been used as clinical standard therapeutic regimen in treatments of colorectal cancer (CRC) and esophageal squamous cell carcinoma (ESCC). To further improve its therapeutic outcomes, FOLFOX was combined with anti-PD-1 antibody to form an advanced chemo-immune combination strategy, which has been proven more efficient in controlling cancer progression and prolonging patients' survival in various clinical trials. However, bad tumor accumulation, relative high toxicity, numerous treatment cycles with high fees and low compliance as well as drug resistance seriously limit the prognosis of FOLFOX regimen. The "all-in-one" formulations, which could precisely delivery multidrug regimen into tumor sites and cells, showed a promising application prospect for targeted drug delivery as well as reducing side effects. However, the design and preparation of the "all-in-one" formulation with high drug encapsulation efficiencies for all drugs was still challenging. Herein, a lipid core-shell nanoparticle codelivery platform was designed for simultaneous encapsulation of variant FOLFOX composed of miriplatin (MiPt), 5-Fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP), calcium folinate (CF) and PD-L1 siRNA (siPD-L1) with high efficiencies, and their synergistic anti-tumor mechanisms were studied, respectively. MiPt, a precursor of OXP, was validated capable of inducing efficient immunogenic cell death (ICD) in this work. Additionally, ICD-mediated release of damage associated molecular patterns functionalized synergistically with PD-L1 silence by siPD-L1 to overcome chemoresistance, reverse suppressive tumor microenvironment and recruit more CD8 + T cells. FdUMP, as the intracellular active form of 5-FU, could induce large amounts of reactive oxygen species to enhance the ICD. CF worked as the sensitizer of FdUMP. The enhanced long-term anti-tumor effect of the prepared "all-in-one" formulation compared to free drug regimen and other controls, was verified in heterotopic CRC mice models and ESCC mice models, providing new thoughts for researchers and showing a promising prospect of translation into clinical applications., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier B.V.)

Endocrine therapy is standard for hormone receptor-positive (HR + ) breast cancer treatment. However, current strategies targeting estrogen signaling pay little attention to estradiol metabolism in the liver and is usually challenged by treatment failure. In a previous study, we demonstrated that the natural compound naringenin (NAR) inhibited HR + breast cancer growth by activating estrogen sulfotransferase (EST) expression in the liver. Nevertheless, the poor water solubility, low bio-barrier permeability, and non-specific distribution limited its clinical application, particularly for oral administration. Here, a novel nano endocrine drug NAR-cell penetrating peptide-galactose nanoparticles (NCG) is reported. We demonstrated that NCG presented specific liver targeting and increased intestinal barrier permeability in both cell and zebrafish xenotransplantation models. Furthermore, NCG showed liver targeting and enterohepatic circulation in mouse breast cancer xenografts following oral administration. Notably, the cancer inhibition efficacy of NCG was superior to that of both NAR and the positive control tamoxifen, and was accompanied by increased hepatic EST expression and reduced estradiol levels in the liver, blood, and tumor tissue. Moreover, few side effects were observed after NCG treatment. Our findings reveal NCG as a promising candidate for endocrine therapy and highlight hepatic EST targeting as a novel therapeutic strategy for HR + breast cancer., (© 2024. The Author(s).)

The early diagnosis and real-time prognosis of cardiovascular diseases (CVDs) at the bedside are important. However, real-time detection of myocardial infarction involves the use of large-scale instrumentation and long test times. Herein, a simple, rapid and sensitive lateral flow immunochromatographic strip (LFIS) based on Yb/Er co-doped NaYF 4 upconversion nanoparticles (UCNPs) was demonstrated for use in the detection of myocardial infarction. First, through heavy Yb/Er doping and an inert NaYF 4 shell coating on the nanoparticles, the surface-related luminescence quenching effect of UCNPs was eliminated to enhance the upconversion luminescence. Second, through uniform coating of a SiO 2 layer on the UCNPs, the biological affinity was improved to couple UCNPs and antibody proteins. Finally, through modification and activation with a specific antibody protein (serum amyloid A (SAA)), the UCNPs exhibited intense upconversion luminescence and high specificity when applied as a lateral flow immunochromatographic strip (LFIS). The developed UC-LFIS was highly sensitive (0.1 μg mL -1 ) and specific for detecting SAA in only 10 μL of serum. The UC-LFIS holds great potential for the early diagnosis and prognosis of CVDs.

Background: The current approach for treating colorectal cancer favors the use of drug and gene combination therapy, and targeted nano-systems are gaining considerable attention for minimizing toxicity and improving the efficacy of anticancer treatment. The aim of this study was to develop ligand-modified, irinotecan and gene co-loaded lipid-polymer hybrid nanocarriers for targeted colorectal cancer combination therapy., Methods: Hyaluronic acid modified, irinotecan and gene co-loaded LPNs (HA-I/D-LPNs) were prepared using a solvent-evaporation method. Their average size, zeta potential, drug and gene loading capacity were characterized. The in vitro and in vivo gene transfection and anti-tumor ability of this nano-system were evaluated on colorectal cancer cells and mice bearing colorectal cancer model., Results: HA-I/D-LPNs had a size of 182.3 ± 5.1, over 80% drug encapsulation efficiency and over 90% of gene loading capacity. The peak plasma concentration (C max ) and half-life (T 1/2 ) achieved from HA-I/D-LPNs were 41.31 ± 1.58 μg/mL and 12.56 ± 0.67 h. HA-I/D-LPNs achieved the highest tumor growth inhibition efficacy and the most prominent transfection efficiency in vivo., Conclusion: HA-I/D-LPNs exhibited the most remarkable tumor inhibition efficacy and best gene transfection efficiency in the tumor, which could prove the effects of the drug and gene combination therapy., Competing Interests: The authors report no conflict of interest in this paper., (© 2020 Wang et al.)

The detection and treatment of cancer cells at an early stage are crucial for prolonging the survival time and improving the quality of life of patients. Upconversion nanoparticles (UCNPs) have unique physical and chemical advantages and likely provide a platform for detecting and treating cancer cells at an early stage. In this paper, the principle of UCNPs as chemical sensors based on fluorescence resonance energy transfer (FRET) has been briefly introduced. Research progress in such chemical sensors for detecting and analyzing bioactive substances and heavy metal ions at the subcellular level has been summarized. The principle of UCNP-based nanoprobe-targeting of cancer cells has been described. The research progress in using nanocomposites for cancer cell detection, namely cancer cell targeted imaging and tissue staining, has been discussed. In the field of cancer treatment, the principles and research progress of UCNPs in photodynamic therapy and photothermal therapy of cancer cells are systematically discussed. Finally, the prospects for UCNPs and remaining challenges to UCNP application in the field of cancer diagnosis and treatment are briefly described. This review provides powerful theoretical guidance and useful practical information for the research and application of UCNPs in the field of cancer., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Combination therapy is a promising strategy to treat cancer due to the synergistic effects. The drug and gene co-delivered systems attract more attention in the field of combination therapy., Materials and Methods: In the present research, poly(ethylene glycol)-ε-poly(caprolactone) block copolymer was used for the co-loading of 5-fluorouracil (5-FU) and gene. The physicochemical characteristics, in vitro and in vivo anticancer, and gene transfection efficiency were tested on colon cancer cells and tumor-bearing mice., Results: 5-FU and gene co-loaded nanocarriers had a size of 145 nm. In vivo gene delivery results showed about 60% of gene-positive cells. Tumor volume of nanocarrier groups at day 21 was around 320 mm 3 , which is significantly smaller compared with free 5-FU group (852 mm 3 ) and control group (1,059 mm 3 ). The maximum 5-FU plasma concentration in nanocarrier groups (49 µg/mL) was significantly greater than free 5-FU (13 µg/mL). At 24 hours, drug level of nanocarrier groups was about 2.8 µg/mL compared with 0.02 µg/mL of free 5-FU., Conclusion: The resulting nanocarriers co-loaded with the anticancer drugs and genes could be considered as a promising nanomedicine for colorectal cancer therapy., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Isoliquiritigenin (ISL), a natural anti-breast cancer dietary compound, has poor delivery characteristics and low bioavailability. In order to promote the therapeutic outcome of ISL, a tumor-targeting lipid-polymer hybrid nanoparticle (NP) system modified by tumor-homing iRGD peptides has been developed. The hybrid NPs were prepared by a modified single-step nanoprecipitation method to encapsulate ISL. iRGD peptides were anchored on the surface by a postinsertion method (ISL-iRGD NPs). The stable lipid-polymer structure of ISL-iRGD NPs, with high encapsulation and loading efficiency, was confirmed. Compared to free ISL and non-iRGD-modified counterparts, ISL-iRGD NPs showed higher cytotoxicity and cell apoptosis against the different type of breast cancer cells. This was attributable to higher cellular accumulation mediated by the iRGD-integrin recognition and the nanoscale effect. More importantly, based on the active tumor-tissue accumulation by iRGD peptides and the prolonged in vivo circulation by the stealth nanostructure, ISL-iRGD NPs displayed higher tumor-growth inhibition efficiency in 4T1-bearing breast-tumor mouse models. Therefore, the constructed iRGD modified lipid-polymer hybrid NPs would provide a promising drug-delivery strategy to improve ISL in anti-breast cancer efficacy., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Increasing evidence has highlighted the pivotal role that intimal macrophage (iMΦ) plays in the pathophysiology of atherosclerotic plaques, which represents an attractive target for atherosclerosis treatment. In this work, to address the insufficient specificity of conventional reconstituted high-density lipoprotein (rHDL) for iMΦ and its limited cholesterol efflux ability, we designed a hyaluronan (HA)-anchored core-shell rHDL. This nanoparticle achieved efficient iMΦ-targeted drug delivery via a multistage-targeting approach, and excellent cellular cholesterol removal. It contained a biodegradable poly (lactic-co-glycolic acid) (PLGA) core within a lipid bilayer, and apolipoprotein A-I (apoA-I) absorbing on the lipid bilayer was covalently decorated with HA. The covalent HA coating with superior stability and greater shielding was favorable for not only minimizing the liver uptake but also facilitating the accumulation of nanoparticles at leaky endothelium overexpressing CD44 receptors in atherosclerotic plaques. The ultimate iMΦ homing was achieved via apoA-I after HA coating degraded by hyaluronidase (HAase) (abundant in atherosclerotic plaque). The multistage-targeting mechanism was revealed on the established injured endothelium-macrophage co-culture dynamic system. Upon treatment with HAase in vitro, the nanoparticle HA-(C)-PLGA-rHDL exhibited a greater cholesterol efflux capacity compared with conventional rHDL (2.43-fold). Better targeting efficiency toward iMΦ and attenuated liver accumulation were further proved by results from ex vivo imaging and iMΦ-specific fluorescence localization. Ultimately, HA-(C)-PLGA-rHDL loaded with simvastatin realized the most potent anti-atherogenic efficacies in model animals over other preparations. Thus, the HAase-responsive HDL-mimetic nanoparticle was shown in this study to be a promising nanocarrier for anti-atherogenic therapy, in the light of efficient iMΦ-targeted drug delivery and excellent function of mediating cellular cholesterol efflux., Competing Interests: The authors report no conflicts of interest in this work.

Despite the significant advancement in making hollow structures, one unsolved challenge in the field is how to engineer hollow structures with specific shapes, tunable compositions, and desirable interior structures. In particular, top-down engineering the interiors inside preformed hollow structures is still a daunting task. In this work, we demonstrate a facile approach for the preparation of a variety of uniform hollow structures, including Cu(2)O@Fe(OH)(x) nanorattles and Fe(OH)(x) cages with various shapes and dimensions by template-engaged redox etching of shape-controlled Cu(2)O crystals. The composition can be readily modulated at different structural levels to generate other interesting structures such as Cu(2)O@Fe(2)O(3) and Cu@Fe(3)O(4) rattles, as well as Fe(2)O(3) and Fe(3)O(4) cages. More remarkably, this strategy enables top-down engineering the interiors of hollow structures as demonstrated by the fabrication of double-walled nanorattles and nanoboxes, and even box-in-box structures. In addition, this approach is also applied to form Au and MnO(x) based hollow structures.

Given its favorable physical and chemical properties, Bismuth vanadate (BiVO4) is a commonly studied metal oxide semiconductor for photocatalytic applications. However, BiVO4 shows a high recombination rate of photogenerated charges and limited charge transport capacity, which can be addressed by doping it with tungsten. To develop a highly efficient tungsten‐doped BiVO4‐based (W‐BiVO4) photocatalyst, it is necessary to control the dopant content, crystal structure, and morphology. These properties are, in turn, governed by the synthesis conditions. This work describes a pioneering method of microwave‐assisted reflux synthesis of W‐BiVO4, using ethanol as solvent and polyvinyl pyrrolidone (PVP) as a capping agent. Thus, it is possible to perform the synthesis procedure in only 30 min at 78°C, obtaining extremely regular monoclinic W‐BiVO4 nanosquares. Furthermore, the experiments showed that the most efficient photocatalyst contains 3% tungsten as the dopant. Moreover, the direct oxidation of rhodamine B by the photogenerated holes plays a crucial role in the degradation mechanism. Finally, we observed that although the addition of PVP promotes control of the morphology, it results in a poorly efficient material. This low efficiency may be related to the formation of a polymeric coating on the surface of the catalyst or to a high amount of oxygen defects. Finally, we show that the unique interaction of microwaves with the species present in the reaction media influences nanoparticle growth. [ABSTRACT FROM AUTHOR]

Chiral perovskite nanocrystals have emerged as an interesting chiral excitonic platform that combines both structural flexibility and superior optoelectronic properties. Despite several recent demonstrations of optical activity in various chiral perovskite nanocrystals, efficient circularly polarized luminescence (CPL) with tunable energies remains a challenge. The chirality imprinting mechanism as a function of perovskite nanocrystal dimensionality remains elusive. Here, atomically thin inorganic perovskite nanoplatelets (NPLs) are synthesized with precise control of layer thickness and are functionalized by chiral surface ligands, serving as a unique platform to probe the chirality transfer mechanism at the organic/perovskite interface. It is found that chirality is successfully imprinted into mono‐, bi‐, and tri‐layer inorganic perovskite NPLs, exhibiting tunable circular dichroism (CD) and CPL responses. However, chirality transfer decreases in thicker NPLs, resulting in decreased CD and CPL dissymmetry factors for thicker NPLs. Aided by large‐scale first‐principles calculations, it is proposed that chirality transfer is mainly mediated through a surface distortion rather than a hybridization of electronic states, giving rise to symmetry breaking in the perovskite lattice and spin‐split conduction bands. The findings described here provide an in‐depth understanding of chirality transfer and design principles for distorted‐surface perovskites for chiral photonic applications. [ABSTRACT FROM AUTHOR]

Herein, a facile and controllable strategy to synthesize self‐hydroxylated TiO2 nanocrystals with promoted photocatalytic activity in hydrogen evolution is demonstrated. Various colors (yellow, light yellow, blueish gray and gray) in appearance are induced by controlling the molar ratio of titanium source to oxidant during the hydrothermal treatment. Compared with commercial P25 TiO2 nanoparticles, the as‐obtained self‐hydroxylated TiO2 nanocrystals exhibit better photocatalytic performance in H2 evolution. Specifically, the maximum hydrogen evolution rate under solar light illumination (10.0 mmol/h/g) is 4.6 times superior to that of P25. The characterization results confirm the presence of abundant hydroxyls resulting from the hydrothermal treatment, which decreases the recombination rate of carriers and the energy barrier of hydrogen formation while facilitates light absorption for promoting photocatalytic performance. [ABSTRACT FROM AUTHOR]

A versatile synthetic method has been developed for the fabrication of Mn3O4 nanocrystals with different sizes and shapes, such as square nanoplates, mesocrystal nanodisks, and nanopolyhedra. Manganese(II) acetate tetrahydrate and hydrazine monohydrate were the only two reactants used in aqueous solution, and no surfactant was employed. The key advantages of our approach are (1) the room-temperature synthesis, (2) the facile operation, (3) the flexibility in shapeand size-control, and (4) the ease of scale-up. The exposed surfaces of the as-prepared nanoparticles were carefully characterized and indexed. The catalytic properties of the nanoplates for the degradation of methylene blue were evaluated in detail. The catalytic properties are closely related to the shape and size of the Mn3O4 nanocrystals, and nanoplates with a size of 50 nm exhibited the best catalytic performance. The magnetic properties were investigated with a superconducting quantum interference device magnetometer. [ABSTRACT FROM AUTHOR]

Atomic force microscopy (AFM) has become a promising tool for not only imaging and measuring matter at the nanoscale [1] but also manipulating and fabricating nano-objects [2], [3]. AFM offers multiple working modes for sensing and actuating with one versatile probe. It can easily switch between scanning and manipulating a nano-object either in an ambient atmosphere or in a liquid environment [4]. One of the important nanoparticle manipulations is the nanoparticle transfer, in which two movements of grasping and transferring are involved. Although the two movements are directly in conflict with the single probe-based mechanism, an AFM-based robotic nanomanipulation system with a virtual nanohand has been developed to solve the conflicting issue of movements. In this article, we show how an AFM-based virtual nanohand is designed to grasp and transfer a nanoparticle at the nanometer scale stably, efficiently, and effectively. [ABSTRACT FROM PUBLISHER]

One of the major limitations for Atomic Force Microscopy (AFM)-based nanomanipulation is that AFM only has one sharp tip as the end-effector, and can only apply a point force to the nanoobject, which makes it extremely difficult to achieve a stable manipulation. For example, the AFM tip tends to slip-away during nanoparticle manipulation due to its small touch area, and there is no available strategy to manipulate a nanorod in a constant posture with a single tip since the applied point force can make the nanorod rotate more easily. In this paper, a robotic nano-hand method is proposed to solve these problems. The basic idea is using a single tip to mimic the manipulation effect that multi-AFM tip can achieve through the planned high speed sequential tip pushing. The theoretical behavior models of nanoparticle and nanorod are developed, based on which the moving speed and trajectory of the AFM tip are planned artfully to form a nano-hand. In this way, the slip-away problem during nanoparticle manipulation can be get rid of efficiently, and a posture constant manipulation for nanorod can be achieved. The simulation and experimental results demonstrate the effectiveness and advantages of the proposed method. [ABSTRACT FROM PUBLISHER]

Abstract: Rare earth doped NaLa(WO4)2 nanoparticles have been prepared by a simply hydrothermal synthesis procedure. The X-ray diffraction (XRD) pattern shows that the Eu3+-doped NaLa(WO4)2 nanoparticles with an average size of 10–30nm can be obtained via hydrothermal treatment for different time at 180°C. The luminescence intensity of Eu3+-doped NaLa(WO4)2 nanoparticles depended on the size of the nanoparticles. The bright upconversion luminescence of the 2mol% Er3+ and 20mol% Yb3+ codoped NaLa(WO4)2 nanoparticles under 980nm excitation could also be observed. The Yb3+–Er3+ codoped NaLa(WO4)2 nanoparticles prepared by the hydrothermal treatment at 180°C and then heated at 600°C shows a 20 times stronger upconversion luminescence than those prepared by hydrothermal treatment at 180°C or by hydrothermal treatment at 180°C and then heated at 400°C. [Copyright &y& Elsevier]

Abstract: The hydrothermal synthesis process and luminescence properties of Ln3+ doped NaY(WO4)2 nanoparticles have been investigated. Nearly spherical Eu3+ doped NaY(WO4)2 nanoparticles can be observed. The luminescence concentration quenching of Eu3+ in the NaY(WO4)2 nanoparticles was found to be similar to that in the NaY(WO4)2 crystals. The upconversion luminescence intensity of the Yb3+–Er3+ codoped NaY(WO4)2 nanoparticles was found to be much stronger than that of the Er3+ doped NaY(WO4)2 nanoparticles. [Copyright &y& Elsevier]

Abstract: A two-step silica deposition process, including prefunctionalization with poly(vinylpyrrolidone) and the following silica deposition, has been used to fabricate silica layer on the surface of nanoscaled silver shell. The influencing parameters of silica coating process were optimized to prevent the precoated silver nanoparticles from desquamating from silica spheres, finally to obtain mono-dispersed silica spheres with silver and silica multilayer films. The resulted silica layer was dense and uniform, its thickness was controllable in the range of 20–50nm. Such coated silica layer can provide improved thermal stability of the SiO2-Ag core-shell structural spheres. [Copyright &y& Elsevier]

Abstract: Silver nanoparticles of 20 and 70nm, respectively, were deposited on the surfaces of submicron silica spheres. Plasma resonances of the submicron silica spheres with dense and uniform silver layer were investigated using UV/vis absorption spectra. It was found that the silver plasma resonance band of the silica–silver core-shell spheres was broadened and shifted to longer wavelength several hundreds nanometers. The dipole–dipole interactions of neighboring silver particles and Mie scattering of silver shell as a whole may serve as the mechanism of such shift and broadening. [Copyright &y& Elsevier]