FvWRKY48 binds to the pectate lyase FvPLA promoter to control fruit softening in Fragaria vesca.

The regulatory mechanisms that link WRKY gene expression to fruit ripening are largely unknown. Using transgenic approaches, we showed that a WRKY gene from wild strawberry (Fragaria vesca), FvWRKY48, may be involved in fruit softening and ripening. We showed that FvWRKY48 is localized to the nucleus and that degradation of the pectin cell wall polymer homogalacturonan, which is present in the middle lamella and tricellular junction zones of the fruit, was greater in FvWRKY48-OE (overexpressing) fruits than in empty vector (EV)-transformed fruits and less substantial in FvWRKY48-RNAi (RNA interference) fruits. Transcriptomic analysis indicated that the expression of pectate lyase A (FvPLA) was significantly downregulated in the FvWRKY48-RNAi receptacle. We determined that FvWRKY48 bound to the FvPLA promoter via a W-box element through yeast one-hybrid, electrophoretic mobility shift, and chromatin immunoprecipitation quantitative polymerase chain reaction experiments, and ß-glucosidase activity assays suggested that this binding promotes pectate lyase activity. In addition, softening and pectin degradation were more intense in FvPLA-OE fruit than in EV fruit, and the middle lamella and tricellular junction zones were denser in FvPLA-RNAi fruit than in EV fruit. We speculated that FvWRKY48 maybe increase the expression of FvPLA, resulting in pectin degradation and fruit softening.

Evolution of m6A-related genes in insects and the function of METTL3 in silkworm embryonic development.

N6-methyladenosine (m6A) plays a key role in many biological processes. However, the function and evolutionary relationship of m6A-related genes in insects remain largely unknown. Here we analysed the phylogeny of m6A-related genes among 207 insect species and found that m6A-related genes are evolutionarily conserved in insects. Subcellular localization experiments of m6A-related proteins in BmN cells confirmed that BmYTHDF3 was localized in the cytoplasm, BmMETTL3, BmMETTL14, and BmYTHDC were localized in the nucleus, and FL2D was localized to both the nucleus and cytoplasm. We examined the expression patterns of m6A-related genes during the embryonic development of Bombyx mori. To elucidate the function of BmMETTL3 during the embryonic stage, RNA sequencing was performed to measure changes in gene expression in silkworm eggs after BmMETTL3 knockdown, as well as in BmN cells overexpressing BmMETTL3. The global transcriptional pattern showed that knockdown of BmMETTL3 affected multiple cellular processes, including oxidoreductase activity, transcription regulator activity, and the cation binding. In addition, transcriptomic data revealed that many observed DEGs were associated with fundamental metabolic processes, including carbon metabolism, purine metabolism, amino acid biosynthesis, and the citrate cycle. Interestingly, we found that knockdown of BmMETTL3 significantly affected Wnt and Toll/Imd pathways in embryos. Taken together, these results suggest that BmMETTL3 plays an essential role in the embryonic development of B. mori, and deepen our understanding of the function of m6A-related genes in insects.

Imaginal disc growth factor is involved in melanin synthesis and energy metabolism in Bombyx mori.

The imaginal disc growth factor (IDGF), belonging to the glycoside hydrolase 18 family, plays an important role in various physiological processes in insects. However, the detail physiological function of IDGF is still unclear. In this study, transcriptome analysis was performed on the fatbody isolated from staged control and BmIDGF mutant silkworm larvae. Transcriptional profiling revealed that the absence of BmIDGF significantly affected differentially expressed genes involved in tyrosine and purine metabolism, as well as multiple energy metabolism pathways, including glycolysis, galactose, starch, and sucrose metabolism. The interruption of BmIDGF caused similar and specific gene expression changes to male and female fatbody. Furthermore, a genome-scale metabolic network integrating metabolomic and transcriptomic datasets revealed 11 pathways significantly altered at the transcriptional and metabolic levels, including amino acid, carbohydrate, uric acid metabolism pathways, insect hormone biosynthesis, and ABC transporters. In conclusion, this multiomics analysis suggests that IDGF is involved in gene-metabolism interactions, revealing its unique role in melanin synthesis and energy metabolism. This study provides new insights into the physiological function of IDGF in insects.

Identification and functional study of detoxification-related genes in response to tolfenpyrad stress in Glyphodes pyloalis Walker (Lepidoptera: Pyralidae).

Glyphodes pyloalis Walker (G. pyloalis) is a common destructive mulberry pest. Due to the long-term and frequent use of insecticides, it has developed tolerance to commonly used insecticides. Tolfenpyrad (TFP) is a novel pyrazole heterocyclic insecticide. In order to understand the TFP detoxification mechanism of G. pyloalis larvae, we first estimated the LC30 dose of TFP for 3rd instar G. pyloalis larvae. Next, we identified genes that were differentially expressed in 3rd instar G. pyloalis larvae treated with TFP compared to the control group by transcriptome sequencing. In total, 86,949,569 and 67,442,028 clean reads were obtained from TFP-treated and control G. pyloalis larvae, respectively. A total of 5588 differentially expressed genes (DEGs) were identified in TFP-treated and control G. pyloalis larvae, of which 3084 genes were upregulated and 2504 genes were downregulated. We analyzed the expression of 43 candidate detoxification enzyme genes associated with insecticide tolerance using qPCR. According to the spatiotemporal expression pattern of DEGs, we found that CYP6ABE1, CYP333A36 and GST-epsilon8 were highly expressed in the midgut, while CarEs14 was strongly expressed in haemolymph. Furthermore, we successfully knocked down these genes by RNA interference. After silencing CYP6ABE1 and CYP333A36, bioassay showed that the mortality rate of TFP-treated G. pyloalis larvae was significantly higher compared to the control group. This study provides a theoretical foundation for understanding the sensitivity of G. pyloalis to TFP and establish the basis for the effective and green management of this pest.

Efficient pH-Responsive Nano-Drug Delivery System Based on Dynamic Boronic Acid/Ester Transformation.

Chemotherapy is currently one of the most widely used treatments for cancer. However, traditional chemotherapy drugs normally have poor tumor selectivity, leading to insufficient accumulation at the tumor site and high systemic cytotoxicity. To address this issue, we designed and prepared a boronic acid/ester-based pH-responsive nano-drug delivery system that targets the acidic microenvironment of tumors. We synthesized hydrophobic polyesters with multiple pendent phenylboronic acid groups (PBA-PAL) and hydrophilic PEGs terminated with dopamine (mPEG-DA). These two types of polymers formed amphiphilic structures through phenylboronic ester linkages, which self-assembled to form stable PTX-loaded nanoparticles (PTX/PBA NPs) using the nanoprecipitation method. The resulting PTX/PBA NPs demonstrated excellent drug encapsulation efficiency and pH-triggered drug-release capacity. In vitro and in vivo evaluations of the anticancer activity of PTX/PBA NPs showed that they improved the pharmacokinetics of drugs and exhibited high anticancer activity while with low systemic toxicity. This novel phenylboronic acid/ester-based pH-responsive nano-drug delivery system can enhance the therapeutic effect of anticancer drugs and may have high potential for clinical transformations.

Zwitterionic Modification of Polyethyleneimine for Efficient In Vitro siRNA Delivery.

Polyethylenimine (PEI) has been widely used in gene delivery. However, its high cytotoxicity and undesired non-specific protein adsorption hinder the overall delivery efficacy and the practical applications of PEI-based gene delivery systems. In this study, we prepared hydrophobically modified PEIs (H-PEIs) via the reaction of octanal with 40% of primary amines in PEI25k and PEI10k, respectively. Two common zwitterionic molecules, 1,3-propanesultone and ß-propiolactone, were then used for the modification of the resulting H-PEIs to construct polycationic gene carriers with zwitterionic properties (H-zPEIs). The siRNA delivery efficiency and cytotoxicity of these materials were evaluated in Hela-Luc and A549-Luc cell lines. Compared with their respective parental H-PEIs, different degrees of zwitterionic modification showed different effects in reducing cytotoxicity and delivery efficiency. All zwitterion-modified PEIs showed excellent siRNA binding capacity, reduced nonspecific protein adsorption, and enhanced stability upon nuclease degradation. It is concluded that zwitterionic molecular modification is an effective method to construct efficient vectors by preventing undesired interactions between polycationic carriers and biomacromolecules. It may offer insights into the modification of other cationic carriers of nucleic acid drugs.

Metal-Free Photosynthesis of Alkylated Benzimidazo[2,1-a]isoquinoline-6(5H)-ones and Indolo[2,1-a]isoquinolin-6(5H)-ones in PEG-200.

A visible-light-induced decarboxylation reaction was developed for the synthesis of alkylated benzimidazo[2,1-a]isoquinoline-6(5H)-ones and indolo[2,1-a]isoquinolin-6(5H)-ones under metal-free conditions. Impressively, metal catalysts and traditionally volatile organic solvents could be effectively avoided.

Hyaluronan-fullerene/AIEgen nanogel as CD44-targeted delivery of tirapazamine for synergistic photodynamic-hypoxia activated therapy.

The therapeutic effect of oxygen-concentration-dependent photodynamic therapy (PDT) can be diminished in the hypoxic environment of solid tumours, the effective solution to this problem is utilising hypoxic-activated bioreduction therapy (BRT). In this research, a biocompatible HA-C60/TPENH2nanogel which can specifically bind to CD44 receptor was developed for highly efficient PDT-BRT synergistic therapy. The nanogel was degradable in acidic microenvironments of tumours and facilitated the release of biological reduction prodrug tirapazamine (TPZ). Importantly, HA-C60/TPENH2nanogel produced reactive oxygen species and consumed oxygen content in the cell to activate TPZ, leading to higher cytotoxicity than the free TPZ did. The intracellular observation of nanogel indicated that the HA-C60/TPENH2nanogel was self-fluorescence for cell imaging. This study applied PDT-BRT to design smart HA-based nanogel with targeted delivery, pH response, and AIEgen feature for efficient cancer therapy.

Design, synthesis, herbicidal activity and CoMFA of aryl-formyl piperidinone HPPD inhibitors.

Isoxazole, nicotinic acid and benzoic acid are important components in many natural products and useful synthons to build macrostructures having valuable biological activities. In continuation of our effort to discover 4-hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) inhibitors and search for active fragments from natural products, a series of substituted aryl-formyl piperidinone derivatives with natural product fragments was rationally designed, synthesized and tested for their herbicidal activity. Compound I-9 was considered the most effective candidate with an IC50 value of 0.260 µM. The molecular docking results showed that the triketone group of compound I-9 forms a bidentate complex with a metal ion, and the benzene ring interacted with Phe424 and Phe381 via π-π stacking, which was similar to the mechanisms of mesotrione. The present work indicates that compound I-9 may serve as a potential lead compound for further development of green HPPD inhibitors.

Highly Efficient Modular Construction of Functional Drug Delivery Platform Based on Amphiphilic Biodegradable Polymers via Click Chemistry.

Amphiphilic copolymers with pendant functional groups in polyester segments are widely used in nanomedicine. These enriched functionalities are designed to form covalent conjugates with payloads or provide additional stabilization effects for encapsulated drugs. A general method is successfully developed for the efficient preparation of functional biodegradable PEG-polyester copolymers via click chemistry. Firstly, in the presence of mPEG as initiator, Sn(Oct)2-catalyzed ring-opening polymerization of the α-alkynyl functionalized lactone with D,L-lactide or ε-caprolactone afforded linear mPEG-polyesters bearing multiple pendant alkynyl groups. Kinetic studies indicated the formation of random copolymers. Through copper-catalyzed azide-alkyne cycloaddition reaction, various small azido molecules with different functionalities to polyester segments are efficiently grafted. The molecular weights, polydispersities and grafting efficiencies of azido molecules of these copolymers were investigated by NMR and GPC. Secondly, it is demonstrated that the resulting amphiphilic functional copolymers with low CMC values could self-assemble to form nanoparticles in aqueous media. In addition, the in vitro degradation study and cytotoxicity assays indicated the excellent biodegradability and low cytotoxicity of these copolymers. This work provides a general approach toward the preparation of functional PEG-polyester copolymers in a quite efficient way, which may further facilitate the application of functional PEG-polyesters as drug delivery materials.

Cu2+ -selective naked-eye 'off-on' fluorescent probe with multisignals: chromaticity, fluorescence, electrochemistry.

In this study, a rhodamine-acetylferrocene conjugate of RBFc was synthesized and then characterized using spectroscopy and single-crystal analysis. The chemosensor RBFc exhibited a marked colour change from colourless to pink after binding to Cu2+ ions. Importantly, under the presence of the other competing cations in aqueous solution, only Cu2+ ions caused spirolactam ring opening in rhodamine B in RBFc, resulting in an enhanced absorbance of ultraviolet light spectra and fluorescence spectra, as well as obvious shifts in cyclic voltammetry curves and differential pulsed voltammetry curves. The novel probe described in this manuscript provides an attractive approach for detecting Cu2+ in the presence of other multisignals.

Cell-Penetrating Peptide Modified PEG-PLA Micelles for Efficient PTX Delivery.

On account of their excellent capacity to significantly improve the bioavailability and solubility of chemotherapy drugs, amphiphilic block copolymer-based micelles have been widely utilized for chemotherapy drug delivery. In order to further improve the antitumor ability and to also reduce undesired side effects of drugs, cell-penetrating peptides have been used to functionalize the surface of polymer micelles endowed with the ability to target tumor tissues. Herein, we first synthesized functional polyethylene glycol-polylactic acid (PEG-PLA) tethered with maleimide at the PEG section of the block polymer, which was further conjugated with a specific peptide, the transactivating transcriptional activator (TAT), with an approved capacity of aiding translocation across the plasma membrane. Then, TAT-conjugated, paclitaxel-loaded nanoparticles were self-assembled into stable nanoparticles with a favorable size of 20 nm, and displayed a significantly increased cytotoxicity, due to their enhanced accumulation via peptide-mediated cellular association in human breast cancer cells (MCF-7) in vitro. But when further used in vivo, TAT-NP-PTX showed an acceleration of the drug's plasma clearance rate compared with NP-PTX, and therefore weakened its antitumor activities in the mice model, because of its positive charge, its elimination by the endoplasmic reticulum system more quickly, and its targeting effect on normal cells leading towards being more toxic. So further modification of TAT-NP-PTX to shield TAT peptide's positive charges may be a hot topic to overcome the present dilemma.

CLD1/SRL1 modulates leaf rolling by affecting cell wall formation, epidermis integrity and water homeostasis in rice.

Leaf rolling is considered as one of the most important agronomic traits in rice breeding. It has been previously reported that SEMI-ROLLED LEAF 1 (SRL1) modulates leaf rolling by regulating the formation of bulliform cells in rice (Oryza sativa); however, the regulatory mechanism underlying SRL1 has yet to be further elucidated. Here, we report the functional characterization of a novel leaf-rolling mutant, curled leaf and dwarf 1 (cld1), with multiple morphological defects. Map-based cloning revealed that CLD1 is allelic with SRL1, and loses function in cld1 through DNA methylation. CLD1/SRL1 encodes a glycophosphatidylinositol (GPI)-anchored membrane protein that modulates leaf rolling and other aspects of rice growth and development. The cld1 mutant exhibits significant decreases in cellulose and lignin contents in secondary cell walls of leaves, indicating that the loss of function of CLD1/SRL1 affects cell wall formation. Furthermore, the loss of CLD1/SRL1 function leads to defective leaf epidermis such as bulliform-like epidermal cells. The defects in leaf epidermis decrease the water-retaining capacity and lead to water deficits in cld1 leaves, which contribute to the main cause of leaf rolling. As a result of the more rapid water loss and lower water content in leaves, cld1 exhibits reduced drought tolerance. Accordingly, the loss of CLD1/SRL1 function causes abnormal expression of genes and proteins associated with cell wall formation, cuticle development and water stress. Taken together, these findings suggest that the functional roles of CLD1/SRL1 in leaf-rolling regulation are closely related to the maintenance of cell wall formation, epidermal integrity and water homeostasis.

Click Chemistry-Assisted Synthesis of a ß-d-Galactose-Targeted SiO2@RC Shell-Core Structure as a Nanoplatform for Metal-Based Complex Delivery.

A facile reversed-phase microemulsion method was used to synthesize shell-core nanospheres of SiO2@RCs (SiO2-encapsuled rare-earth metal complexes). ß-d-Galactose was then grafted onto the surfaces of the nanospheres through the copper(I)-catalyzed azide-alkyne cycloaddition click reaction for targeted delivery. The chemical characteristics and surface profiles of the nanocarriers were investigated by Fourier transform infrared spectroscopy, dynamic light scattering, transmission electron microscopy, and scanning electron microscopy. A high-efficiency microwave synthesis method was applied to prepare five complex cores by the reaction of different rare-earth metal salts with two isomeric ligands, o-CPA (2-chlorophenoxyacetic acid) and m-CPA (3-chlorophenoxyacetic acid). The crystal structures of the five synthesized RC cores were confirmed through X-ray diffraction, which revealed the formulas of five RCs, [Dy( o-CPA)3(H2O)]·H2O RC1, [Ho( o-CPA)3(H2O)]·H2O RC2, 2[Er( m-CPA)3(H2O)]·3H2O RC3, 2[Gd( m-CPA)3(H2O)]·3H2O RC4, and [Ce2( m-CPA)6(H2O)3]·2H2O RC5. An in vitro cell study revealed that all RCs exhibited certain anticancer activities. RC2, in particular, showed the strongest cytotoxicity against HepG2 cells. The enhanced cell permeability and drug retention considerably improved the cytotoxicity of all SiO2@RC2-gal relative to that of RC2. The selective uptake of the ß-d-galactose-conjugated nanospheres by HepG2 cells through mechanisms mediated by cell surface receptors resulted in fewer side effects on extrahepatic tissues. Our contribution provides a novel design concept of a target SiO2@RCs-gal nanocarrier for delivering affordable antitumor complexes in cancer therapy.

Copper nitrate-catalyzed oxidative coupling of unactivated C(sp3)-H bonds of ethers and alkanes with N-hydroxyphthalimide: synthesis of N-hydroxyimide esters.

A copper nitrate-catalyzed cross-dehydrogenative coupling reaction between N-hydroxyphthalimide (NHPI) and ethers/alkanes has been described. The reaction is accomplished smoothly by using simple and green molecular oxygen as the oxidant, providing an alternative for the efficient synthesis of N-alkoxyphthalimides. In addition, it was found that when tert-butyl ethers were used as substrates, unexpected N-hydroxyimide ester derivatives were obtained in moderate to excellent yields. To further understand this unusual transformation, control experiments were performed and a plausible mechanism was proposed.

Expression analysis of different ß-carotenoid hydroxylase gene families in stress response in Dunaliella viridis.

ß-carotenoid hydroxylase (CHYB) is an important rate-limiting enzyme in the biosynthesis of plant carotenoid. In this study, chyb1 and chyb2, two gene families in Dunaliella viridis were obtained by RNA-seq. The fragment of promoters of CHYB family genes, 1 080 bp for chyb1 (GenBank No. KY012338) and 1 155 bp for chyb2 (GenBank No. KY012339) were cloned by the Genome Walking Technology, respectively. Cis-acting elements of two promoters were analyzed by Plantcare soft. The results show that the chyb1 gene promoter contains more cis-acting elements in responses to abiotic stresses, such as methyl jasmonate, arachidonic acid, acetylsalicylic acid, and so on. On the other hand, the chyb2 promoter contains more cis-acting elements in response to light stress. qRT-PCR results show that the mRNA expression levels of CHYBs are modulated by their promoters, and different CHYB gene families response to distinct stresses.

Spectral Analysis of Interaction between Human Telomeric G-Quadruplex and Liliflorin A, the First Lignan Derivative Interacted with G-Quadruplex DNA.

Human telomeric G-quadruplex is a four-stranded structure folded by guanines (G) via Hoogsteen hydrogen bonding. The ligands which stabilize the G-quadruplex are often telomerase inhibitors and may become antitumor agents. Here, the interaction between a lignan derivative liliflorin A and human telomeric sequence dGGG (TTAGGG)3G-quadruplex HTG21 were examined by CD, FRET, and NMR spectroscopic methods. In addition, Molecular Docking was used to study the binding of liliflorin A to dTAGGG (TTAGGG)3 G-quadruplex HTG23. The CD data showed that liliflorin A enhanced HTG21 T(m). The T(m) value of G-quadruplex was enhanced 3.2 degrees C by 4.0 µmol x L(-1) liliflorin A in FRET. The NMR spectra of HTG21 showed vivid alteration after reacting with liliflorin A in 3 hours. Molecular Docking suggested liliflorin A bound to the wide groove of HTG23 at G9, G10, G16 and G17. Liliflorin A was the first lignan derivative that could stabilize HTG21 selectively and provided a new candidate for antitumor drug design targeting on human telomeric G-quadruplex.

Balancing Industry and Drug Policy Objectives in the Pharmaceutical Sector: The Case of China.

Objectives This article assessed the balance between industry and drug policy objectives in the pharmaceutical sector in China. Methods The articles were mainly identified through databases such as Elsevier, Google Scholar, and SpringerLink, among others. Related articles were mainly separated into three categories: studies on drug policies, studies related to China's new health-care reform policy, and studies concerning patent policies. Results A relatively healthy environment for continuous innovation and drug patent protection in the pharmaceutical industry has been created in China, and the public's drug benefits have also significantly improved. However, the balance between industrial and drug policy objectives in the pharmaceutical sector in China requires additional attention. Discussion and conclusions The results suggest that the government should pay more attention to incentivizing enterprises' innovation, but the current Essential Medicines System in China has limited innovation. Hence, the mechanism for selecting essential medicines should be reformed, and certain appropriate and reasonably innovative medicines should be included. Additionally, medicine coverage, especially the coverage of essential drugs for primary care should be expanded to improve public health benefits. Furthermore, the pharmaceutical industry should be incorporated into the prospective National Drug Policy to achieve a balance between public benefits and pharmaceutical industry development in the future.

[Transcriptome analysis of Dunaliella viridis].

In order to understand the gene information, function, haloduric pathway (glycerolipid metabolism) and related key genes for Dunaliella viridis, we used Illumina HiSeqTM 2000 high-throughput sequencing technology to sequence its transcriptome. Trinity soft was used to assemble the data to form transcripts. Based on the Clusters of Orthologous Groups (COG), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG ) databases, we carried out functional annotation and classification, pathway annotation, and the opening reading fragment (ORF) sequence prediction of transcripts. The key genes in the glycerolipid metabolism were analyzed. The results suggested that 81,593 transcripts were found, and 77,117 ORF sequences were predicted, accounting for 94.50% of all transcripts. COG classification results showed that 16,569 transcripts were assigned to 24 categories. GO classification annotated 76,436 transcripts. The number of transcripts for biologcial processes was 30,678, accounting for 40.14% of all transcripts. KEGG pathway analysis showed that 26,428 transcripts were annotated to 317 pathways, and 131 pathways were related to metabolism, accounting for 41.32% of all annotated pathways. Only one transcript was annotated as coding the key enzyme dihydroxyacetone kinase involved in the glycerolipid pathway. This enzyme could be related to glycerol biosynthesis under salt stress. This study further improved the gene information and laid the foundation of metabolic pathway research for Dunaliella viridis.

Novel aromatic moieties-modified poly(glycidyl amine)s with potent siRNA delivery and cancer treatment effect.

The development of safe and effective delivery systems is critical for the clinical applications of siRNA-based therapeutics. Polymer-based vectors have garnered significant attention owing to their structural flexibility and functional tunability. Polyethyleneimine (PEI) has been extensively studied for nucleic acid delivery; nevertheless, its high cytotoxicity has posed challenges for clinical applications. In this study, we have reported poly(glycidyl amine) (PGAm), a linear PEI analogue, demonstrating remarkable siRNA delivery efficacy and improved biocompatibility. By introducing three aromatic moieties (tyrosine, p-hydroxybenzenepropanoic acid, and phenylalanine) at varying ratios to further modify PGAms, we successfully constructed a library comprising 36 PGAm-based carriers. In vitro evaluations revealed that PGAm-based carriers exhibited significantly enhanced biocompatibility and reduced non-specific protein absorption in comparison to PEI25k. Among them, 10 modified PGAms achieved a knockdown of target gene expressions exceeding 80%, and 26 modified PGAms maintained over 70% cell viability when utilized for the in vitro delivery of siRNA to HeLa cells. Explorations into the structure-activity relationship of PGAm-based polyplex nanoparticles (NPs) indicated that the siRNA delivery efficacy of NPs depended on factors such as the molecular weight of PGAm precursors, the type of modifying moieties, and the modification ratio. Furthermore, it was demonstrated that two top-performing NPs, namely 2T100/siLuc and 2A50/siLuc, exhibited potent silencing of target genes in tumors following i.v. injection into mice bearing HeLa-Luc xenografts. The in vivo efficacy of the selected NPs was further validated by a remarkable anti-cancer effect when employed for the delivery of siRNA targeting polo-like kinase 1 (siPLK1) to mice with PC-3 xenograft tumors. The intravenous administration of NPs resulted in a substantial inhibition of tumor growth without significant toxicity. These findings demonstrate the feasibility of employing PGAm in siRNA delivery and provide valuable insights for the development of efficient siRNA carriers based on PGAm.