Cross-kingdom RNA interference mediated by insect salivary microRNAs may suppress plant immunity.

Communication between insects and plants relies on the exchange of bioactive molecules that traverse the species interface. Although proteinic effectors have been extensively studied, our knowledge of other molecules involved in this process remains limited. In this study, we investigate the role of salivary microRNAs (miRNAs) from the rice planthopper Nilaparvata lugens in suppressing plant immunity. A total of three miRNAs were confirmed to be secreted into host plants during insect feeding. Notably, the sequence-conserved miR-7-5P is specifically expressed in the salivary glands of N. lugens and is secreted into saliva, distinguishing it significantly from homologues found in other insects. Silencing miR-7-5P negatively affects N. lugens feeding on rice plants, but not on artificial diets. The impaired feeding performance of miR-7-5P-silenced insects can be rescued by transgenic plants overexpressing miR-7-5P. Through target prediction and experimental testing, we demonstrate that miR-7-5P targets multiple plant genes, including the immune-associated bZIP transcription factor 43 (OsbZIP43). Infestation of rice plants by miR-7-5P-silenced insects leads to the increased expression of OsbZIP43, while the presence of miR-7-5P counteracts this upregulation effect. Furthermore, overexpressing OsbZIP43 confers plant resistance against insects which can be subverted by miR-7-5P. Our findings suggest a mechanism by which herbivorous insects have evolved salivary miRNAs to suppress plant immunity, expanding our understanding of cross-kingdom RNA interference between interacting organisms.

Comparative transcriptomic analysis of salivary glands between the zoophytophagous Cyrtorhinus lividipennis and the phytozoophagous Apolygus lucorum.

BACKGROUND: Saliva plays a crucial role in shaping the feeding behavior of insects, involving processes such as food digestion and the regulation of interactions between insects and their hosts. Cyrtorhinus lividipennis serves as a predominant natural enemy of rice pests, while Apolygus lucorum, exhibiting phytozoophagous feeding behavior, is a destructive agricultural pest. In this study, a comparative transcriptome analysis, incorporating the published genomes of C.lividipennis and A.lucorum, was conducted to reveal the role of salivary secretion in host adaptation. RESULTS: In contrast to A.lucorum, C.lividipennis is a zoophytophagous insect. A de novo genome analysis of C.lividipennis yielded 19,706 unigenes, including 16,217 annotated ones. On the other hand, A.lucorum had altogether 20,111 annotated genes, as obtained from the published official gene set (20,353 unigenes). Functional analysis of the top 1,000 salivary gland (SG)-abundant genes in both insects revealed that the SG was a dynamically active tissue engaged in protein synthesis and secretion. Predictions of other tissues and signal peptides were compared. As a result, 94 and 157 salivary proteins were identified in C.lividipennis and A.lucorum, respectively, and were categorized into 68 and 81 orthogroups. Among them, 26 orthogroups were shared, potentially playing common roles in digestion and detoxification, including several venom serine proteases. Furthermore, 42 and 55 orthogroups were exclusive in C.lividipennis and A.lucorum, respectively, which were exemplified by a hyaluronidase in C.lividipennis that was associated with predation, while polygalacturonases in A.lucorum were involved in mesophyll-feeding patterns. CONCLUSIONS: Findings in this study provide a comprehensive insight into saliva secretions in C.lividipennis and A.lucorum via a transcriptome approach, reflecting the intricate connections between saliva secretions and feeding behaviors. It is found that conserved salivary secretions are involved in shaping the overlapping feeding patterns, while a plethora of unique salivary secretions may drive the evolution of specific feeding behaviors crucial for their survival. These results enhance our understanding of the feeding mechanisms in different insects from the perspective of saliva and contribute to future environmentally friendly pest control by utilizing predatory insects.

Healable, Recyclable, and Multifunctional Soft Electronics Based on Biopolymer Hydrogel and Patterned Liquid Metal.

Recent years have witnessed the rapid development of sustainable materials. Along this line, developing biodegradable or recyclable soft electronics is challenging yet important due to their versatile applications in biomedical devices, soft robots, and wearables. Although some degradable bulk hydrogels are directly used as the soft electronics, the sensing performances are usually limited due to the absence of distributed conducting circuits. Here, sustainable hydrogel-based soft electronics (HSE) are reported that integrate sensing elements and patterned liquid metal (LM) in the gelatin-alginate hybrid hydrogel. The biopolymer hydrogel is transparent, robust, resilient, and recyclable. The HSE is multifunctional; it can sense strain, temperature, heart rate (electrocardiogram), and pH. The strain sensing is sufficiently sensitive to detect a human pulse. In addition, the device serves as a model system for iontophoretic drug delivery by using patterned LM as the soft conductor and electrode. Noncontact detection of nearby objects is also achieved based on electrostatic-field-induced voltage. The LM and biopolymer hydrogel are healable, recyclable, and degradable, favoring sustainable applications and reconstruction of the device with new functions. Such HSE with multiple functions and favorable attributes should open opportunities in next-generation electronic skins and hydrogel machines.

211At-Labeled Polymer Nanoparticles for Targeted Radionuclide Therapy of Glucose-Dependent Insulinotropic Polypeptide Receptor (GIPR)-Overexpressed Cancer.

Targeted radionuclide therapy (TRT) provides new and safe opportunities for cancer treatment and management with high precision and efficiency. Here we have designed a novel semiconducting polymer nanoparticle (SPN)-based radiopharmaceutical (211At-MeATE-SPN-GIP) for TRT against glucose-dependent insulinotropic polypeptide receptor (GIPR)-positive cancers to further explore the applications of nanoengineered TRT. 211At-MeATE-SPN-GIP was engineered via nanoprecipitation, followed by its functionalization with a glucose-dependent insulinotropic polypeptide (GIP) to target GIPR and deliver 211At for α therapy. The therapeutic effect and biological safety of 211At-MeATE-SPN-GIP were investigated using GIPR-overexpressing human pancreatic cancer CFPAC-1 cells and CFPAC-1-bearing mice. In this work, 211At-MeATE-SPN-GIP was produced with a radiochemical yield of 43% and radiochemical purity of 98%, which exhibited a specifically high uptake in CFPAC-1 cells, inducing cell cycle arrest at the G2/M phase and extensive DNA damage. In the CFPAC-1-bearing tumor model, 211At-MeATE-SPN-GIP exhibited high therapeutic efficiency, with no obvious side effects. The GIPR-specific binding of 211At-MeATE-SPN-GIP combined with effective inhibition of tumor growth and fewer side effects compared to control suggests that 211At-MeATE-SPN-GIP TRT holds great potential as a novel nanoengineered TRT strategy for patients with GIPR-positive cancer.

Pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor in children with acute leukaemia.

AIMS: This open-label, phase I study evaluated the pharmacokinetics and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for the treatment of chemotherapy-induced neutropenia in children with acute leukaemia. METHODS: PEG-rhG-CSF was administered as a single 100 mcg/kg (3 mg maximum dose) subcutaneous injection at the end of each chemotherapy period when neutropenia occurred. Blood samples were obtained from patients treated with PEG-rhG-CSF. PEG-rhG-CSF serum concentrations were determined by an enzyme-linked immunosorbent assay. Population pharmacokinetic (PPK) analysis was implemented using the nonlinear mixed-effects model. Short-term safety was evaluated through adverse events collection (registered at clinicaltrials.gov identifier: 03844360). RESULTS: A total of 16 acute leukaemia patients (1.8-13.6 years) were included, of whom two (12.5%) had grade 3 neutropenia, six (37.5%) had grade 4 neutropenia, and eight (50.0%) had severe neutropenia. For PPK modelling, 64 PEG-rhG-CSF serum concentrations were obtainable. A one-compartment model with first-order elimination was used for pharmacokinetic data modelling. The current weight was a significant covariate. The median (range) of clearance (CL) and area under the serum concentration-time curve (AUC) were 5.65 (1.49-14.45) mL/h/kg and 16514.75 (6632.45-54423.30) ng·h/mL, respectively. Bone pain, pyrexia, anaphylaxis and nephrotoxicity were not observed. One patient died 13 days after administration, and the objective assessment of causality was that an association with PEG-rhG-CSF was "possible". CONCLUSIONS: The AUC of PEG-rhG-CSF (100 mcg/kg, 3 mg maximum dose) in paediatric patients with acute leukaemia were similar to those of PEG-rhG-CSF (100 mcg/kg) in children with sarcoma. PEG-rhG-CSF is safe, representing an important therapeutic option for chemotherapy-induced neutropenia in paediatric patients with acute leukaemia.

Semiconducting polymer nano-radiopharmaceutical for combined radio-photothermal therapy of pancreatic tumor.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a devastatingly malignant tumor with a high mortality. However, current strategies to treat PDAC generally have low efficacy and high side-effects, therefore, effective treatment against PDAC remains an urgent need. RESULTS: We report a semiconducting polymer nano-radiopharmaceutical with intrinsic photothermal capability and labeling with therapeutic radioisotope 177Lu (177Lu-SPN-GIP) for combined radio- and photothermal therapy of pancreatic tumor. 177Lu-SPN-GIP endowed good stability at physiological conditions, high cell uptake, and long retention time in tumor site. By virtue of combined radiotherapy (RT) and photothermal therapy (PTT), 177Lu-SPN-GIP exhibited enhanced therapeutic capability to kill cancer cells and xenograft tumor in living mice compared with RT or PTT alone. More importantly, 177Lu-SPN-GIP could suppress the growth of the tumor stem cells and reverse epithelial mesenchymal transition (EMT), which may greatly reduce the occurrence of metastasis. CONCLUSION: Such strategy we developed could improve therapeutic outcomes over traditional RT as it is able to ablate tumor with relatively lower doses of radiopharmaceuticals to reduce its side effects.

The Role of Salivary Pepsin in the Diagnosis of Gastroesophageal Reflux Disease (GERD) Evaluated Using High-Resolution Manometry and 24-Hour Multichannel Intraluminal Impedance-pH Monitoring.

BACKGROUND The Lyon Consensus classification confirms or rules out gastroesophageal reflux disease (GERD). The refractory symptoms of patients with GERD taking proton pump inhibitors (PPIs) are challenging in clinical practice. Salivary pepsin concentration was proposed as a diagnostic biomarker for GERD. We aimed to determine the diagnostic value of salivary pepsin concentration for patients with conclusive GERD, based on the Lyon classification, and the correlation of salivary pepsin concentration with parameters of high-resolution manometry and 24-h multichannel intraluminal impedance-pH in patients with PPI-refractory symptoms. MATERIAL AND METHODS Saliva samples obtained from 130 patients who were suspicious for GERD and had PPI-refractory symptoms were used for pepsin determination using the enzyme-linked immunosorbent assay. All patients underwent upper gastrointestinal endoscopy, high-resolution manometry, 24-h multichannel intraluminal impedance, and pH recording and were classified as conclusive GERD, inconclusive GERD, and evidence against GERD groups according to Lyon classification. RESULTS Salivary pepsin concentration was 8.2 ng/mL (3.8-17.8 ng/mL), 4.0 ng/mL (2.3-6.1 ng/mL), and 2.4 ng/mL (2.2-3.1 ng/mL) in conclusive GERD, inconclusive GERD, and evidence against GERD groups, respectively (P<0.001), and had a negative correlation with distal mean nocturnal baseline impedance and positive correlations with acid exposure time, total number of reflux events, and esophagogastric junction type. The area under the ROC curve of salivary pepsin for conclusive GERD was 0.76 (0.68-0.84), with a sensitivity of 76.36% and a specificity of 63.41% for conclusive GERD diagnosis at a cut-off value of 4.21 ng/mL. CONCLUSIONS Salivary pepsin test had moderate diagnostic value for conclusive GERD by Lyon classification in patients with PPI-refractory symptoms.

Two-in-One Chemogene Assembled from Drug-Integrated Antisense Oligonucleotides To Reverse Chemoresistance.

Combinatorial chemo and gene therapy provides a promising way to cure drug-resistant cancer, since the codelivered functional nucleic acids can regulate drug resistance genes, thus restoring sensitivity of the cells to chemotherapeutics. However, the dramatic chemical and physical differences between chemotherapeutics and nucleic acids greatly hinder the design and construction of an ideal drug delivery system (DDS) to achieve synergistic antitumor effects. Herein, we report a novel approach to synthesize a nanosized DDS using drug-integrated DNA with antisense sequences (termed "chemogene") to treat drug-resistant cancer. As a proof of concept, floxuridine (F), a typical nucleoside analog antitumor drug, was incorporated in the antisense sequence in the place of thymine (T) based on their structural similarity. After conjugation with polycaprolactone, a spherical nucleic acid (SNA)-like two-in-one chemogene can be self-assembled, which possesses the capabilities of rapid cell entry without the need for a transfection agent, efficient downregulation of drug resistance genes, and chronic release of chemotherapeutics for treating the drug-resistant tumors in both subcutaneous and orthotopic liver transplantation mouse models.

Fibronectin Facilitates Enterovirus 71 Infection by Mediating Viral Entry.

Fibronectin (FN) is a high-molecular-weight extracellular matrix protein that contains the RGDS motif, which is required to bind to integrins. Synthetic RGDS peptides have been reported to compete with FN to bind to the cell surface and inhibit the function of FN. Here, we identified that synthetic RGDS peptides significantly inhibit human enterovirus 71 (EV71) infection in cell cultures. In addition, mice treated with RGDS peptides and infected with EV71 had a significantly higher survival rate and a lower viral load than the control group. Because RGDS peptides affect the function of FN, we questioned whether FN may play a role in virus infection. Our study indicates that overexpression of FN enhanced EV71 infection. In contrast, knockout of FN significantly reduced viral yield and decreased the viral binding to host cells. Furthermore, EV71 entry, rather than intracellular viral replication, was blocked by FN inhibitor pretreatment. Next, we found that FN could interact with the EV71 capsid protein VP1, and further truncated-mutation assays indicated that the D2 domain of FN could interact with the N-terminal fragment of VP1. Taken together, our results demonstrate that the host factor FN binds to EV71 particles and facilitates EV71 entry, providing a potential therapy target for EV71 infection.IMPORTANCE Hand, foot, and mouth disease outbreaks have occurred frequently in recent years, sometimes causing severe neurological complications and even death in infants and young children worldwide. Unfortunately, no effective antiviral drugs are available for human enterovirus 71 (EV71), one of the viruses that cause hand, foot, and mouth disease. The infection process and the host factors involved remain unknown, although several receptors have been identified. In this study, we found that the host factor fibronectin (FN) facilitated EV71 replication by interacting with EV71 particles and further mediated their entry. The RGDS peptide, an FN inhibitor, significantly inhibited EV71 replication in both RD cells and mice. In conclusion, our research identified a new host factor involved in EV71 infection, providing a new potential antiviral target for EV71 treatment.

Pepsin in Saliva as a Diagnostic Marker for Gastroesophageal Reflux Disease: A Meta-Analysis.

BACKGROUND Gastroesophageal reflux disease (GERD) is very common. Salivary pepsin detection has previously been considered as a method for GERD diagnosis. We performed a meta-analysis to investigate the utility of salivary pepsin assay as a diagnostic tool of GERD. MATERIAL AND METHODS PubMed, Web of Science, the Cochran Library, and EMBASE (from January 1980 to 23 October 2018) were searched for pepsin in saliva for GERD diagnosis. We summarized the retrieved specificity, sensitivity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), diagnostic odds ratio (DOR), and receiver operating characteristic (ROC) curves data in the meta-analysis. RESULTS In final analysis, a total of 5 studies were included. The summary sensitivity, specificity, NLR, and PLR were 0.60 (95% CI 0.41-0.76), 0.71 (95% CI 0.51-0.86), 0.56 (95% CI 0.34-0.93), and 2.1 (95% CI 1.1-4.1), respectively. The pooled DOR was 4 (95% CI 1.0-11.0) and area under the ROC was 0.70 (95% CI 0.66-0.74). CONCLUSIONS The meta-analysis showed that pepsin in saliva has moderate diagnostic value for GERD, and is not as helpful as previously thought.

A Crosslinked Nucleic Acid Nanogel for Effective siRNA Delivery and Antitumor Therapy.

Functional siRNAs are employed as cross-linkers to direct the self-assembly of DNA-grafted polycaprolactone (DNA-g-PCL) brushes to form spherical and nanosized hydrogels via nucleic acid hybridization in which small interfering RNAs (siRNAs) are fully embedded and protected for systemic delivery. Owing to the existence of multivalent mutual crosslinking events inside, the crosslinked nanogels with tunable size exhibit not only good thermostability, but also remarkable physiological stability that can resist the enzymatic degradation. As a novel siRNA delivery system with spherical nucleic acid (SNA) architecture, the crosslinked nanogels can assist the delivery of siRNAs into different cells without any transfection agents and achieve the gene silencing effectively both in vitro and in vivo, through which a significant inhibition of tumor growth is realized in the anticancer treatment.

Screening and Functional Analyses of Nilaparvata lugens Salivary Proteome.

Most phloem-feeding insects secrete gelling and watery saliva during the feeding process. However, the functions of salivary proteins are poorly understood. In this study, our purpose was to reveal the components and functions of saliva in a rice sap-sucking insect pest, Nilaparvata lugens. The accomplishment of the whole genome and transcriptome sequencing in N. lugens would be helpful for elucidating the gene information and expression specificity of the salivary proteins. In this study, we have, for the first time, identified the abundant protein components from gelling and watery saliva in a monophagous sap-sucking insect species through shotgun proteomic detection combined with the genomic and transcriptomic analysis. Eight unknown secreted proteins were limited to N. lugens, indicating species-specific saliva components. A group of annexin-like proteins first identified in the secreted saliva displayed different domain structure and expression specificity with typical insect annexins. Nineteen genes encoding five annexin-like proteins, six salivaps (salivary glands-specific proteins with unknown function), seven putative enzymes, and a mucin-like protein showed salivary gland-specific expression pattern, suggesting their importance in the physiological mechanisms of salivary gland and saliva in this insect species. RNA interference revealed that salivap-3 is a key protein factor in forming the salivary sheath, while annexin-like5 and carbonic anhydrase are indispensable for N. lugens survival. These novel findings will greatly help to clarify the detailed functions of salivary proteins in the physiological process of N. lugens and elucidate the interaction mechanisms between N. lugens and the rice plant, which could provide important targets for the future management of rice pests.

Cationic lioposomes with folic acid as targeting ligand for gene delivery.

In our previous Letter, we have carried out the synthesis of a novel DDCTMA cationic lipid which was formulated with DOPE for gene delivery. Herein, we used folic acid (FA) as targeting ligand and cholesterol (Chol) as helper lipid instead of DOPE for enhancing the stability of the liposomes. These liposomes were characterized by dynamic laser scattering (DLS), transmission electron microscopy (TEM) and agarose gel electrophoresis assays of pDNA binding affinity. The lipoplexes were prepared by using different weight ratios of DDCTMA/Chol (1:1, 2:1, 3:1, 4:1) liposomes and different concentrations of FA (50-200µg/mL) combining with pDNA. The transfection efficiencies of the lipoplexes were evaluated using pGFP-N2 and pGL3 plasmid DNA against NCI-H460 cells in vitro. Among them, the optimum gene transfection efficiency with DDCTMA/Chol (3:1)/FA (100µg/mL) was obtained. The results showed that FA could improve the gene transfection efficiencies of DDCTMA/Chol cationic liposome. Our results also convincingly demonstrated FA (100µg/mL)-coated DDCTMA/Chol (3:1) cationic liposome could serve as a promising candidate for the gene delivery.

Biodegradable DNA-Brush Block Copolymer Spherical Nucleic Acids Enable Transfection Agent-Free Intracellular Gene Regulation.

By grafting multiple DNA strands onto one terminus of a polyester chain, a DNA-brush block copolymer that can assemble into micelle structure is constructed. These micelle spherical nucleic acids have a density of nucleic acids that is substantively higher than linear DNA block copolymer structures, which makes them effective cellular transfection and intracellular gene regulation agents.

Glucose-responsive polymer vesicles templated by α-CD/PEG inclusion complex.

Polymeric nanoparticles with glucose-responsiveness are of great interest in developing a self-regulated drug delivery system. In this work, glucose-responsive polymer vesicles were fabricated based on the complexation between a glucosamine (GA)-containing block copolymer PEG45-b-P(Asp-co-AspGA) and a phenylboronic acid (PBA)-containing block copolymer PEG114-b-P(Asp-co-AspPBA) with α-CD/PEG45 inclusion complex as the sacrificial template. The obtained polymer vesicles composed of cross-linked P(Asp-co-AspGA)/P(Asp-co-AspPBA) layer as wall and PEG chains as both inner and outer coronas. The vesicular morphology was observed by transmission electron microscopy (TEM), and the glucose-responsiveness was investigated by monitoring the variations of hydrodynamic diameter (Dh) and light scattering intensity (LSI) in the polymer vesicle solution with glucose using dynamic light scattering (DLS). Vancomycin as a model drug was encapsulated in the polymer vesicles and sugar-triggered drug release was carried out. This kind of polymer vesicle may be a promising candidate for glucose-responsive drug delivery.

Recent developments in ureteral stent: Substrate material, coating polymer and technology, therapeutic function.

The ureteral stent is an effective treatment for clinical ureteral stricture following urological surgery, and the functional coating of the stent could effectively inhibit bacterial colonization and other complications. The present review provides an analysis and description of the materials used in ureteral stents and their coatings. Emphasis is placed on the technological advancements of functional coatings, taking into consideration the characteristics of these materials and the properties of their active substances. Furthermore, recent advances in enhancing the therapeutic efficacy of functional coatings are also reviewed. It is anticipated that this article will serve as a valuable reference providing insights for future research development on new drug-loaded ureteral stents.

Controlled assemblies of gold nanorods in PVA nanofiber matrix as flexible free-standing SERS substrates by electrospinning.

Under control: Controlled assemblies of gold nanorods in a poly(vinyl alcohol) (PVA) nanofiber matrix with tunable optical properties can be achieved by using electrospinning. The resultant assemblies can be used as substrates for surface-enhanced Raman spectroscopy (SERS). This work provides a facile way to control alignment of anisotropic nanostructures in a polymer nanofiber matrix and generates new assemblies with interesting properties.

Dialysis nanoprecipitation of polystyrene nanoparticles.

Using a facile dialysis nanoprecipitation method, nanoparticles of several hundred nanometers have been successfully generated from a "traditional," non-biodegradable polymer, that is, polystyrene. The effect of initial polymer concentration inside the dialysis membrane, as well as the polymer/solvent system and the ionic strength (electrolyte concentration) of the dialysis solution, on nanoparticle size is examined. A nucleation-aggregation mechanism has been provided to explain the observed trends. Furthermore, we determine the zeta potential as a function of ionic strength for the generated nanoparticles and show that anionic charging may be present in the system.

Copackaging photosensitizer and PD-L1 siRNA in a nucleic acid nanogel for synergistic cancer photoimmunotherapy.

Packaging multiple drugs into a nanocarrier with rational design to achieve synergistic cancer therapy remains a challenge due to the intrinsically varied pharmacodynamics of therapeutic agents. Especially difficult is combining small-molecule drugs and macromolecular biologics. Here, we successfully graft pheophorbide A (PPA) photosensitizers on DNA backbone at predesigned phosphorothioate modification sites. The synthesized four PPA-grafted DNAs are assembled into a tetrahedron framework, which further associates with a programmed death ligand-1 (PD-L1) small interfering RNA (siRNA) linker through supramolecular self-assembly to form an siRNA and PPA copackaged nanogel. With dual therapeutic agents inside, the nanogel can photodynamically kill tumor cells and induce remarkable immunogenic cell death. Also, it simultaneously silences the PD-L1 expression of the tumor cells, which substantially promotes the antitumor immune response and leads to an enhanced antitumor efficacy in a synergistic fashion.

Complexing the Pre-assembled Brush-like siRNA with Poly(ß-amino ester) for Efficient Gene Silencing.

Small interfering RNA (siRNA) has been emerging as a highly selective and effective pharmaceutics for treating broad classes of diseases. However, the practical application of siRNA agent is often hampered by its poor crossing of the cellular membrane barrier and ineffective releasing from endosome to cytoplasm, leading to low gene silencing efficacy for clinical purposes. Thus far, cationic lipid and polymer-based vectors have been extensively explored for gene delivery. Yet condensing the rigid and highly negatively charged siRNA duplex to form a stable complex vehicle usually requires a large load of cationic carriers, prone to raising the toxicity issue for delivery. Herein, we develop a simple strategy that can efficiently condense the siRNAs into nanoparticle vehicles for target gene regulation. In this approach, we first employ a DNA-grafted polycaprolactone (DNA-g-PCL) brush as template to organize the small rigid siRNAs into a large brush-like structure (siRNA-brush) through nucleic acid hybridization. Then, the siRNA-brush assembly is condensed by an ionizable and biodegradable polymer (poly(ß-amino ester), PBAE) under acidic buffer condition to form a stable nanoparticle for siRNA delivery. Compared to the free siRNAs with poor complexing capability with PBAE, the large brush-like siRNA assemblies with more complicated topological architecture significantly promotes their electrostatic interaction with PBAE, enabling the formation of complexed nanoparticles at low weight ratio of polymer to siRNA. Additionally, PBAE/siRNA-brush complexes exhibit good biocompatibility and stability under physiological condition, as well as enhanced cellular internalization. When equipped with functional siRNAs, the obtained delivery system demonstrates excellent downregulation of target genes both in vitro and in vivo, through which the progression of hypertrophic scars can be retarded with negligible adverse effects in an xenografted mouse model.