Cell membrane-engineered nano-delivery systems have evolved as a promising strategy to enhance drug bioavailability, offering an alternative for reversing drug resistance in cancer therapy. Herein, a formulated nano-liposome that fabricated by hybridizing cisplatin-resistant A549 cell line (A549/cis) cancer cell membrane and phospholipids for co-delivery of cisplatin and nuclear protein zeste homolog 2 (EZH2)-targeting peptide EIP103, referred to as cLCE, was developed. In vitro results indicated that the formulated nano-liposome can efficiently inhibit A549/cis cancer cell invasion and metastasis through the down-regulation of N-cadherin and vimentin proteins. Mechanistic studies demonstrated that the reduction of nerve growth factor receptor (NGFR) levels and the increase of peroxisome proliferator-activated receptor γ (PPARγ) levels achieved by EIP103 may contribute to the reversal of cisplatin resistance. In vivo results demonstrated that the encapsulation of both cisplatin and EIP103 within cLCE leads to increased intratumoral accumulation and prolonged survival in A549/cis cancer-bearing mice as compared to the individual drugs alone. This can be attributed to the enhanced tumor homing capability of cLCE achieved through the presence of inherited membrane proteins derived from A549/cis cells. Taken together, this study may provide a highly promising therapeutic strategy to improve clinical treatments for cisplatin-resistance non-small-cell lung cancer (NSCLC) as well as other malignant cancers.
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Chemotherapy remains one of the most prevailing strategies for cancer treatment. However, its treatment effect is hampered by drug resistance, nonspecific tumor targeting, and severe toxic side effects. Combination chemotherapy with synergistic effect has become an attractive tumor therapy. N6-methyladenosine (m6A) regulators determine the fate of m6A-modified transcripts and play vital roles in cancer development and drug resistance. Gene therapy such as small interfering RNA (siRNA) is a promising strategy to reduce the abnormal gene expression of m6A regulators. However, its poor selectivity and high systemic toxicity necessitate the use of delivery vectors to target specific cells and tissues. Here, we constructed a dual-functional targeted nanodrug platform for the synergetic m6A-associated epigenetic regulation and chemotherapy of ovarian cancer. We encapsulated siRNA targeting the m6A reader YT521-B homology (YTH) N6-methyladenosine RNA-binding protein 1 (YTHDF1) and docetaxel (DTX), the first-line chemotherapeutic agent of ovarian cancer, into mesenchymal stem cell-derived small extracellular vesicles (MsEVs). This nanosystem exhibits significant tumor targeting and endo/lysosomal escape of siYTHDF1. It effectively depletes YTHDF1 and suppresses the protein translation of eukaryotic translation initiation factor 3 subunit C (EIF3C) in an m6A-dependent manner. The combination of YTHDF1-targeting epigenetic regulation significantly enhances the anti-tumor effect of DTX and effectively inhibits ovarian cancer progression without causing significant systemic toxicity. This co-delivery nanoplatform offers a promising approach for combinational cancer treatment, showing improved anti-tumor efficacy through the synergistic effects of epigenetic regulation and chemotherapeutic inhibition.
We have determined the binding strengths between ribonucleotides of adenine (A), guanine (G), uracil (U), and cytosine (C) in homogeneous single-stranded ribonucleic acids (ssRNAs) and homo-decapeptides consisting of 20 common amino acids. We use a bead-based fluorescence assay for these measurements in which decapeptides are immobilized on the bead surface and ssRNAs are in solutions. The results provide a molecular basis for analyzing selectivity, specificity, and polymorphisms of amino-acid–ribonucleotide interactions. Comparative analyses of the distribution of the binding energies reveal unique binding strength patterns assignable to each pair of amino acid and ribonucleotide originating from the chemical structures. Pronounced favorable (such as Arg–G) and unfavorable (such as Met–U) binding interactions can be identified in selected groups of amino acid and ribonucleotide pairs that could provide basis to elucidate energetics of amino-acid–ribonucleotide interactions. Such interaction selectivity, specificity, and polymorphism manifest the contributions from RNA backbone, RNA bases, as well as main chain and side chain of the amino acids. Such characteristics in peptide–RNA interactions might be helpful for understanding the mechanism of protein–RNA specific recognition and the design of RNA nano-delivery systems based on peptides and their derivatives.
Fullerene derivatives as a kind of star carbon materials have received intense investigation because of their three-dimensional shape, anisotropic electron mobility, and high electron affinity. Indeed, the cutting-edge developments of fullerene nanomaterials have had a tremendous impact on a wide range of applications, such as organic solar cells, field effect transistors, and photodetectors. To explore their full potential applications, research into fullerene-based multilevel nanostructures relying on hierarchical interactions from bottom to top is rapidly expanding. It is of great theoretical and practical significance to prepare multilevel fullerene nanostructures with structural and properties controlled by optimizing the influencing factors. This review would offer several aspects including the chemical structures of organic molecules and the nanostructures of the organic molecules and fullerene-organic complexes. Whether monolayers or multilayers, fullerene molecules tend to fall into a space of suitable size, in which the located positions are affected by the intermolecular interactions. For the covered surfaces, fullerenes are more likely to approach the electron-withdrawing units through the donor–acceptor and charge transfer interaction. Through the implementation of this review, an exhaustive analysis on the chemical modification, including the molecular backbone and substituents, preformed network synergies, and adsorption sites is presented. In addition, the relationship between the molecules and structures that illustrates the importance of the molecular design for the controlled fullerenes hybrid nanostructures can be further understood based on the results of the joined experimental and computational investigations.
When the dimensionality of layered compounds decreases to the physical limit, ultimate two-dimensional (2D) anisotropy and/or quantum confinement effects may lead to extraordinary physicochemical attributes. Here, we report single-layer Rh nanosheets (NSs) exhibiting ultrahigh peroxidase-like activity, far exceeding that of horseradish peroxidase (HRP) and of most known layered nanomaterial-based peroxidase mimics. Considering per NS as an active subunit, the Rh NSs displayed a catalytic rate constant (Kcat) as high as 4.45 × 105 s–1 to H2O2, two orders of magnitude higher than those of HRP and Rh nanoparticles. The high atom efficiency of the Rh NSs can be attributed to the full exposure of surface-active Rh atoms, which greatly facilitates electron transfer and formation of superoxide anions, representing reactive oxygen species in the catalytic process. As a proof-of-concept application, the Rh NSs were successfully used as peroxidase mimics for the colorimetric detection of H2O2 and xanthine, with high sensitivity and selectivity. Moreover, a simple, rapid, and sensitive Rh-based paper sensor for ascorbic acid was also developed. In summary, this work provides a novel example of single-layer metallic NSs for biosensing.
We report a facile protocol for the one-pot preparation of monodisperse Pd nanoparticles (NPs) supported on ultrathin NiCl2 nanosheets (NSs). The effective protocol can be described as in situ reduction–oxidation–assembly to create Pd/NiCl2 nanocomposites and is applicable for the development of stable yet highly active Pd-based heterogeneous catalysts for organic transformations. The Pd/NiCl2 composite displayed synergistically enhanced catalytic activity, high stability, and good recyclability for the tested model oxidation reaction. The in situ nucleation and growth of NiCl2 NS around Pd NPs guaranteed a clean metal–support interface and greatly facilitated the catalytic reaction. This work provides a novel synthesis method for supported Pd nanocomposites suitable for many important applications.
For the design and optimization of functional peptides, unravelling the structures of individual building blocks as well as the properties of the ensemble is paramount. TTR1, derived from human transthyretin, is a fibril-forming peptide implicated in diseases such as familial amyloid polyneuropathy and senile systemic amyloidosis. The functional peptide TTR1-RGD, based on a TTR1 scaffold, was designed to specifically interact with cells. Here, we used scanning tunneling microscopy (STM) to analyze the assembly structures of TTR1-related peptides with both the reverse sequence and the modified forward sequence. The sitespecific analyses show the following: ⅰ) The TTR1 peptide is involved in assembly, nearly covering the entire length within the ordered β-sheet structures. ⅱ) For TTR1-RGD peptide assemblies, the TTR1 motif forms the ordered β-sheet while the RGDS motif adopts a flexible conformation allowing it to promote cell adhesion. The key site is clearly identified as the linker residue Gly13. ⅲ) Close inspection of the forward and reverse peptide assemblies show that in spite of the difference in chemistry, they display similar assembling characteristics, illustrating the robust nature of these peptides. iv) Glycine linker residues are included in the β-strands, which strongly suggests that the sequence could be optimized by adding more linker residues. These garnered insights into the assembled structures of these peptides help unravel the mechanism driving peptide assemblies and instruct the rational design and optimization of sequenceprogrammed peptide architectures.
Enhancing the activity of Pt-based nanocatalysts is of great significance yet a challenge for the oxygen reduction reaction (ORR). In this work, a series of porous Pt/Ag nanoparticles (NPs) were fabricated from regular PtxAg100–x (x = 25, 50, 75) octahedra by a facile and economical dealloying process. Remarkable enhancement in multiple enzyme-mimic activities related to ORR was observed for the dealloyed Pt50Ag50 (D-Pt50Ag50) NPs. This effect can be attributed to the resulting Pt-rich surface structure, increased surface area, and a synergistic effect of Pt and Ag atoms in the D-Pt50Ag50 NPs. Furthermore, the D-Pt50Ag50 NPs exerted excellent antibacterial effects on two model bacteria (gram-negative Escherichia coli and gram-positive Staphylococcus aureus). The present work represents a significant advance in the exploration of the relation between controllable synthesis of high-quality nanoalloys and their novel catalytic properties for various promising applications, including catalysts, biosensors, and biomedicine.
The assembling behavior and electronic properties of asymmetric tris(phthalocyaninato) lutetium tripledecker sandwich complex molecules (Lu2Pc3) on highly oriented pyrolytic graphite (HOPG) surfaces have been studied by scanning tunneling microscopy/spectroscopy (STM/STS) methods. Phase transitions were observed at different bias polarities, involving an ordered packing arrangement with fourfold symmetry at negative bias and an amorphous arrangement at positive bias. Molecular switching behaviour for individual Lu2Pc3 molecules was reported here according to the bias-polarity-induced flipping phenomena and the peak shift in dI/dV versus V curves at different voltage scanning directions. The sensitive response of the strong intrinsic molecular dipole to an external electric field is proposed to be responsible for molecular switching of Lu2Pc3 at the solid/liquid interface.