Search

Current nucleic acid delivery methods have not achieved efficient, non-toxic delivery of miRNAs with tumor-specific selectivity. In this study, a new delivery system based on light-inducible gold-silver-gold, core-shell-shell (CSS) nanoparticles is presented. This system delivers small nucleic acid therapeutics with precise spatiotemporal control, demonstrating the potential for achieving tumor-specific selectivity and efficient delivery of miRNA mimics. The light-inducible particles leverage the photothermal heating of metal nanoparticles due to the local surface plasmonic resonance for controlled chemical cleavage and release of the miRNA mimic payload. The CSS morphology and composition result in a plasmonic resonance within the near-infrared (NIR) region of the light spectrum. Through this method, exogenous miR-34a-5p mimics are effectively delivered to human squamous cell carcinoma TE10 cells, leading to apoptosis induction without adverse effects on untransformed keratinocytes in vitro. The CSS nanoparticle delivery system is tested in vivo in Foxn1nu athymic nude mice with bilateral human esophageal TE10 cancer cells xenografts. These experiments reveal that this CSS nanoparticle conjugates, when systemically administered, followed by 850 nm light emitting diode irradiation at the tumor site, 6 h post-injection, produce a significant and sustained reduction in tumor volume, exceeding 87% in less than 72 h., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

As a highly crystalline and renewable natural polymer nanomaterial, chitin nanocrystals (ChNCs) have attracted intense interest in the biomedical field. The structure of a ChNC is composed of an acetylglucosamine unit containing two hydroxyl groups and an acetyl group. The acetyl group can be converted to the active amino group through deacetylation, which is under the condition of maintaining the rod-like morphology and high crystalline property and is beneficial for the following modification and potential application. We investigated the relationship between different treatments and varied crystallinities of the modified ChNC, which obtained surface amino groups and aldehyde groups and retained high crystallinity. The natural biomolecules were covalently immobilized on the surface of the ChNC. The etherification was performed based on the hydroxyl groups. Based on the amino groups and the aldehyde groups, the carboxyamine and Knoevenagel condensation reactions were realized on ChNCs. Finally, natural biomolecule-modified ChNCs showed no or low cytotoxicity, antibacterial properties, and high antioxidant properties, which extended their potential biomedical applications.

With the rapid aging of the global population, the prevalence of neurodegenerative diseases has become a significant concern, with Alzheimer's disease (AD) being the most common. However, the clinical trials of many drugs targeting AD have failed due to the challenges posed by the blood-brain barrier (BBB), which makes intracerebral administration of drugs difficult. However, nanoparticles (NPs) may aid in the delivery of such drugs. NPs are materials with sizes between 1-100 nm that offer several advantages, such as improving biocompatibility, prolonging half-life, transporting large molecules, crossing the BBB to deliver to the central nervous system, and exhibiting good targeting ability. In addition to drug delivery, NPs also have excellent diagnostic potential, and multifunctional NPs can integrate the advantages of diagnosis, targeting, and treatment. This mini-review article provides an overview of NPs, including the composition of the carrier, strategies for crossing the BBB, and different targets of AD pathology, with the aim of providing guidance for the development prospects of NPs.

Encapsulation of therapeutic molecules into nanocarrier is an extensively explored strategy to treat cancer more effectively. In this study, pH-responsive targeting dual-agent delivery nanoparticles were prepared, into which hydrophilic doxorubicin hydrochloride (DOX) and hydrophobic curcumin (CUR) were entrapped. Tyrosine (Tyr) was grafted onto poly(aspartic acid) (PASP) to produce PASP-Tyr, the following reaction between hyaluronic acid (HA) and ethylenediamine (EDA) modified PASP-Tyr formed the nanocarrier HA-EDA-PASP-Tyr (HEPT), and the loading capacity was up to 50.9 ± 4.3% for CUR and 26.0 ± 1.9% for DOX. The spherical HEPT with the mean particle size of 142.9 ± 11.4 nm expanded and deformed into petaloid pattern with an increased size of about 2 µm when triggered by the acidic microenvironment. In vitro anticancer activity evaluation revealed that the co-loaded (DOX+CUR)@HEPT nanoparticles presented higher cytotoxicity against HCT-116 cells compared with that of the free combination of (DOX+CUR). Confocal laser scanning microscopy observation indicated that HEPT carrier promoted cellular uptake of drugs by means of active targeting capacity of HA ligand. With high loading capacity and tailored carrier structure, the nanoparticles formulations may offer a new strategy for cancer treatment.

In this study, a new type of polypeptide, crosslinked methoxy poly(ethylene glycol)-g-poly(aspartic acid)-g-tyrosine (CPPT), was synthesized via a green and simple one-pot polymerization method. With the disulfide-crosslinked interlayer and the CaP shell, the pH and redox dual-sensitive polypeptide-based organic-inorganic hybrid nanoparticles encapsulated curcumin (Cur) into the hydrophobic core of micelles and loaded doxorubicin hydrochloride (DOX) on the hydrophilic segment of micelles as well as CaP shell. The spherical Cur- and DOX-loaded nanoparticles (CPPT@CaP-CD) showed a hydrodynamics size of about 157.9 ± 3.9 nm. The premature leakage of drugs from the nanoparticles at physiological pH was efficiently restrained because of the enhanced structure integrity, whereas at acidic and hypoxia microenvironment the release of both drugs was promoted due to the rapid dissolution of the CaP shell and the break of the disulfide crosslinked network, facilitating the stimuli-responsive controllable drugs release. In vitro anticancer activity evaluation revealed that the co-loaded nanoparticles presented higher cytotoxicity against A549 cells compared with that of the free combination of Cur + DOX. Confocal laser scanning microscopy observation indicated that more DOX and Cur were released into the nucleus triggered by the up-regulated intracellular glutathione (GSH) concentration and decreased pH, displaying enhanced cell uptake. The self-assembling polypeptide-based dual-sensitive drug co-delivery system could be a promising platform for efficient chemotherapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Despite evidence that microRNAs (miRNAs) are essential in modulating tumorigenesis, a major challenge in cancer treatment is to achieve tumor-specific selectivity and efficient yet safe delivery of miRNAs in vivo. In this study, we have developed a light-inducible silver nanoparticle nucleic acid delivery system that demonstrates precise spatiotemporal control, high cellular uptake, low cytotoxicity, escape from endosomes and release of functional miRNA into the cytosol. Using this approach, we delivered exogenous miR-148b to induce apoptosis in Ras-expressing keratinocytes and murine squamous cell carcinoma cells while avoiding cytotoxicity in untransformed keratinocytes. When administered to transgenic mice with HRas G12V -driven skin tumors, a single dose of silver nanoparticle conjugates followed by 415 nm LED irradiation at the tumor site caused a rapid and sustained reduction in tumor volume by 92.8%, recruited T cells to the tumor site, and acted as a potent immunomodulator by polarizing the cytokine balance toward Th1 both locally and systemically. In summary, our results demonstrate that spatiotemporal controlled miR-148b mimic delivery can promote tumor regression efficiently and safely., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

To obtain magnetic nanoparticles with high magnetic heating efficiency and rapid in vivo clearance, this study utilized an improved linear response theory model to theoretically simulate the specific absorption rate (SAR) value versus the particle size of cobalt ferrite nanoparticles (CFNPs). An accurate SAR curve consistent with experimental results was obtained using cubes instead of spheres as the shape of CFNPs, given that cube was closer to the actual shape of prepared CFNPs. Under the guidance of simulation, we predicted and prepared water-soluble cubic CFNPs of 10-13 nm in size, with an ultrathin surface coating less than 1 nm in thickness. These CFNPs were experimentally verified to have high magnetic heating efficiency and rapid in vivo clearance rate. Our CFNPs of 11.8 nm in size had a high intrinsic loss power of 12.11 nHm 2 /kg. Most of the cells were killed within 30 min under magnetic heating with CFNPs. In an in vivo study, these CFNPs can heat a tumor area to 45 °C (ΔT > 9 °C) within 120 s under a weak alternating magnetic field (27 kA/m, 115 kHz). Notably, these CFNPs had significant tumor inhibition rate in vivo and can be cleared from the body by more than 64% within 2 weeks, demonstrating excellent rapid in vivo clearance. This result was close to the clearance level of the magnetic resonance imaging contrast agent Feridex. Therefore, our CFNPs had high magnetic heating efficiency and rapid in vivo clearance rate, indicating their great potential for future clinical applications., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

To improve the tumor synergistic therapeutic effects of carrier-free dual-drug delivery systems and realize ultralow dose administration, we developed a tumor targeting and high-efficiency synergistic chemotherapy system (HA-Gn@DPGn NPs) based on polyvinyl alcohol (PVA) reinforced gossypolone (Gn) and doxorubicin (DOX) π-π stacking nanoparticles (DPGn NPs), in which PVA filled the gaps between Gn and DOX and bridged Gn and DOX tightly. Hyaluronic acid modifier hyaluronic acid-gossypolone (HA-Gn) was covered on the surface of DPGn NPs to form HA-Gn@DPGn NPs that procured active targeting properties. This system presented a spherical shape with a uniform hydrodynamic size of 87 ± 6.8 nm, a high drug loading of 80.31%, and high stability. FTIR and UV spectra demonstrated that HA-Gn was covered on the surface of the system and showed significant π-π stacking properties. A considerably low combination index of Gn and DOX (0.1862) was determined at an ultra-low dose of DOX under a Gn : DOX ratio of 50 : 1. HA-Gn@DPGn NPs also demonstrated excellent tumor synergistic therapeutic efficacy (TIR > 87%) at an ultralow dose of DOX and Gn. This system demonstrates high tumor comprehensive synergistic therapeutic efficacy at an ultralow drug dose with multiple favorable therapeutic characteristics, including negligible side effects, tumor targeting ability and thermal-responsive drug release, and thus has considerable potential for tumor synergistic therapy.

Myosin light-chain kinase (MLCK) is a widely known kinase that controls the contraction of muscle cells. Whether MLCK is involved in the endocytosis of nanoparticles (NPs) has not been reported yet. NPs attract interest in many fields; most of them can induce autophagy and cytotoxicity after entering cells via endocytosis. In this study, we found that MLCK inhibitors, ML-7 and ML-9, abolished the endocytosis of silver NPs and yttrium oxide NPs in HeLa cells, and subsequently attenuated the autophagy induction and cytotoxicity caused by the NPs treatment. This is the first report that MLCK inhibitors acted as an endocytosis inhibitor and abolished the cell entry of NPs, which provided a new method for inhibiting the endocytosis of NPs.

The possible adverse effects of engineered nanomaterials on human health raise increasing concern as our research on nanosafety intensifies. Upon entry into a human body, whether intended for a theranostic purpose or through unintended exposure, nanomaterials tend to accumulate in the liver, leading to hepatic damage. A variety of nanoparticles, including rare earth upconversion nanoparticles (UCNs), have been reported to elicit hepatotoxicity, in most cases through inducing immune response or activating reactive oxygen species. Many of these nanoparticles also induce autophagy, and autophagy inhibition has been shown to decrease UCN-induced liver damage. Herein, using UCNs as a model engineered nanomaterial, this study uncovers a critical role for Kupffer cells in nanomaterial-induced liver toxicity, as depletion of Kupffer cells significantly exacerbates UCN-induced liver injury. Furthermore, UCN-induced prodeath autophagy in Kupffer cells, and inhibition of autophagy with 3-MA, a well-established chemical inhibitor of autophagy, enhances Kupffer cell survival and further abrogates UCN-induced liver toxicity. The results reveal the critical importance of Kupffer cell autophagy for nanoparticle-induced liver damage, and inhibition of autophagy may constitute a novel strategy for abrogating nanomaterial-elicited liver toxicity., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The development of an efficient targeted drug delivery system into cells is an important subject for the advancement of drug carriers. In this study, a novel hepatocyte-targeted delivery system with glycyrrhizin (GL) surface modification based on N-caproyl chitosan (CCS) has been developed., Method: CCS was synthesized by acylation of amino group of chitosan, and GL was oxidized to be conjugated to the surface of N-caproyl chitosan nanoparticles (CCS-NPs-GL). The synthesized nanoparticles were first characterized for their morphology, particle size, zeta potential, in vitro stability in plasma, tissue distribution, and hepatocyte-targeting uptake in vivo., Results: The obtained results showed that the spherical and discrete nanoparticles prepared with oxidized GL/CCS ratio of 0.14:1 (w/w) exhibited a positive electrical charge and associated adriamycin quite efficiently (association efficiency: 87.5%). The prepared nanoparticles also possessed dimensional and GL surface-binding stability and slow release property in plasma in vitro. The biodistribution of these particles after intravenous injections in mice revealed accumulating drug concentrations in the liver, spleen, and lungs while decreasing drug concentrations in the heart and kidney. The content of adriamycin-loaded CCS-NPs-GL in the liver was 1.6 times higher than that of non-GL-modified CCS-NPs. Furthermore, in vivo uptake of CCS-NPs-GL by rat hepatocytes showed 2.1 times higher nanoparticle uptake compared with non-GL-modified CCS-NPs, which suggested that CCS-NPs-GL were preferentially distributed in hepatocytes by a ligand-receptor interaction., Conclusion: This article indicated that CCS-NPs-GL was a stable and effective drug delivery vehicle for hepatocyte targeting.

The aim of the present work was to investigate the potential utility of chitosan nanoparticles surface modified with glycyrrhizin (CS-NPs-GL) as new hepatocyte-targeted delivery vehicles. For this purpose, chitosan nanoparticles (CS-NPs) were prepared previously by ionic gelation process and glycyrrhizin was oxidized by sodium periodate to be conjugated to the surface of CS-NPs. The CS-NPs-GL obtained were first characterized for their morphology, particle size, zeta potential, association efficiency and in vitro release of adriamycin (ADR), using as a model drug. The nanoparticles were also labeled with rhodamine B isothiocyanate and their interaction with rat hepatocytes was examined by flow cytometry (FCM) and confocal laser microscopy (CLSM). The spherical nanoparticles prepared with oxidized GL/CS ratio of 0.14:1 (w/w) were in the 147.2nm size range, and exhibited a positive electrical charge (+9.3mV), and associated ADR quite efficiently (association efficiency: 91.7%) and showed lower extent of release (28% over 72h) in vitro. FCM and CLSM studies showed that CS-NPs-GL were preferentially accumulated in hepatocytes and the cellular uptake amount were 4.9 times more than that in hepatic nonparenchymal cells, and the uptake process was dependent on incubation time and dose of nanoparticles, which indicated that the internalization of these nanoparticles into hepatocytes was mostly mediated by a ligand-receptor interaction. In conclusion, CS-NPs-GL as a promising hepatocyte-targeted delivery carrier holds promise for further effective studies.

To further improve the comprehensive therapeutic effect for large tumors, tumor cell membrane‐camouflaged molecular stacking composite nanoparticles (APGn@Mem NPs) are prepared by molecular stacking of chemotherapeutic drug gossypolone (Gn), thermodynamic agent (2,2'‐azobis[2‐(2‐imidazolin‐2‐yl) propane] dihydrochloride (AIPH)), polyvinyl alcohol, and phase change material lauric acid, which show a clear core–shell structure with a size of 65 ± 9.8 nm, high drug loading, low toxicity, homologous targeting, and thermal‐responsive release property. A type of micro‐electrothermal needle (MEN) with precise temperature control in situ (temperature range: mean value T ± 7 °C) is designed as the assistant heating system for APGn@Mem NPs. Subsequently, an elaborate tumor combination therapy strategy of electrothermal‐thermodynamic‐chemo trimodal combination therapy is developed through APGn@Mem NPs combined with the temperature control of MEN. Under MEN heating in situ, AIPH is rapidly released and generates abundant free radicals for short‐term electrothermal and thermodynamic therapy, while the release of Gn is relatively slow for long‐term chemotherapy. For large tumors (≈300 mm3) of nude mice, such combination therapy achieves remarkable comprehensive therapeutic efficacy with the 16‐day tumor inhibition rate of 99.89% and the 60‐day tumor recurrence rate of 20%, indicating this combination therapy has the prominent advantage and potential application in future. [ABSTRACT FROM AUTHOR]

This study investigated the effects of 1 wt% SiC nanoparticles addition on the microstructures and mechanical properties of Mg9Al–1Si (wt%) alloy subjected to equal channel angular pressing (ECAP). Results showed that addition of SiC nanoparticles could refine matrix grain, Mg17Al12 and Mg2Si phase of as-cast alloy, but the Mg17Al12 phase still exhibited network structure and the morphology of Mg2Si phase was still Chinese-script type. During the ECAP process, network Mg17Al12 and Chinese-script shaped Mg2Si phases were partially broken down into fine particles (∼10 µm) and much finer particles (∼2 µm) respectively. In particular, these Mg17Al12 and Mg2Si particles were uniform distribution in ECAPed Mg9Al–1Si–1SiC composite. The well-distributed particles and the existence of SiC nanoparticles could promote the formation of fine DRXed grains through enhanced grain boundary pinning. During tensile testing at room temperature, ECAPed Mg9Al–1Si–1SiC composite exhibit optimal mechanical properties, the ultimate tensile strength and elongation to failure were reached to 255 MPa and 7.9%, respectively. Furthermore, at elevated temperature of 150 °C, the tensile strength and elongation to failure were considerably increased compared to an ECAPed, SiC-free Mg9Al–1Si alloy. [ABSTRACT FROM PUBLISHER]

This study focused on the microwave-assisted one-step synthesis and evaluation of visible light-sensitized Ce, N, and P tri-doped titanium dioxide nanoparticles loaded on activated carbon (TiO 2 /AC) photocatalyst for the photocatalytic degradation of naphthalene. X-ray photoelectron spectroscopy (XPS) of the samples showed the presence of both Ce 3+ and Ce 4+ oxidation states. A red shift of the absorption edge in the UV–visible spectra was observed when Ce, N, or P was doped in the band gap of TiO 2 . Ce, N, and P tri-doped TiO 2 /AC exhibited the highest photocatalytic activity (97.9%) and rate constant under visible-light irradiation. The photocatalyst could be applied in environmental purification as indicated by its excellent performance. The possible synergetic mechanism for the photodegradation was also discussed. This study provides an effective strategy for synthesizing novel high-performance TiO 2 nanocomposite photocatalyst to degrade naphthalene. [ABSTRACT FROM AUTHOR]

This study employed a precipitation method to synthesize zinc oxide@quaternised chitosan nanoparticles (ZnO@QAC NPs) containing different concentrations of zinc oxide, namely ZnO@QAC-2, ZnO@QAC-4, and ZnO@QAC-6. Subsequently, these nanoparticles were incorporated into matrices consisting of gelatine (Gn) and polyvinyl alcohol (PVA) separately, which were prepared by casting to form a biodegradable film. We assessed the physicochemical properties of ZnO@QAC NPs and physicochemical characteristics, antioxidant properties, antimicrobial activity and grape preservation efficacy of the film. Compared to the control group, the films showed a reduction in water vapor permeability by >9.38 %, an increase in tensile strength by over 51.95 %, over 70 % scavenging of ABTS free radicals, and good biocompatibility. Additionally, the antimicrobial activity of the films containing ZnO@QAC-6 increased by 37.6 %. In the grape preservation experiment, the weight loss of grapes wrapped in ZnO@QAC-2 film was reduced by 40.13 % on day 15 compared to unwrapped grapes. These results demonstrate that ZnO@QAC/PVA/Gn films have considerable potential for food packaging applications. [Display omitted] • ZnO particles modified with quaternised chitosan were successfully prepared. • ZnO@QAC NPs, poly(vinyl alcohol) and gelatin had good compatibility. • The composite film has good antioxidant, biodegradable and antimicrobial properties. • The film inhibited the loss of water and texture in grapes well. • The composite film has great potential for application in the food sector. [ABSTRACT FROM AUTHOR]