Chromosome-level genome assembly of Chouioia cunea Yang, the parasitic wasp of the fall webworm.

Chouioia cunea Yang 1989 is a parasitic wasp of many lepidopteran insects during their pupal stage, and has been successfully used to control pests such as the fall webworm Hyphantria cunea. Here we reported the chromosome-level genome of C. cunea by using short (MGI-SEQ), long (Oxford Nanopore), chromatin-linked (Hi-C) sequencing reads and transcriptomic data, representing the first chromosome-level genome of parasitic wasps of the family Eulophidae. The total assembly length is 171.99 Mb, containing 6 pesudo-chromosomes with a GC content of 36.89% and the scaffold/contig N50 length of 31.70/26.52 Mb. The BUSCO completeness of the assembly was estimated to be 98.7%. A total of 12,258 protein-coding genes (PCGs), 10,547 3'-UTRs, and 10,671 5'-UTRs were annotated. This high-quality genome is an important step toward a better understanding of the genomes of the Eulophidae (Chalcidoidea), and will serve as a valuable resource for analyses of phylogenetic relationships and the evolution of Hymenoptera.

The chromosome-level genome of Chinese praying mantis Tenodera sinensis (Mantodea: Mantidae) reveals its biology as a predator.

BACKGROUND: The Chinese praying mantis, Tenodera sinensis (Saussure), is a carnivorous insect that preys on a variety of arthropods and small vertebrates, including pest species. Several studies have been conducted to understand its behavior and physiology. However, there is limited knowledge about the genetic information underlying its genome evolution, digestive demands, and predatory behaviors. FINDINGS: Here we have assembled the chromosome-level genome of T. sinensis, representing the first sequenced genome of the family Mantidae, with a genome size of 2.54 Gb and scaffold N50 of 174.78 Mb. Our analyses revealed that 98.6% of BUSCO genes are present, resulting in a well-annotated assembly compared to other insect genomes, containing 25,022 genes. The reconstructed phylogenetic analysis showed the expected topology placing the praying mantis in an appropriate position. Analysis of transposon elements suggested the Gypsy/Dirs family, which belongs to long terminal repeat (LTR) transposons, may be a key factor resulting in the larger genome size. The genome shows expansions in several digestion and detoxification associated gene families, including trypsin and glycosyl hydrolase (GH) genes, ATP-binding cassette (ABC) transporter, and carboxylesterase (CarE), reflecting the possible genomic basis of digestive demands. Furthermore, we have found 1 ultraviolet-sensitive opsin and 2 long-wavelength-sensitive (LWS) opsins, emphasizing the core role of LWS opsins in regulating predatory behaviors. CONCLUSIONS: The high-quality genome assembly of the praying mantis provides a valuable repository for studying the evolutionary patterns of the mantis genomes and the gene expression profiles of insect predators.

NIR-absorbing dye functionalized hollow mesoporous silica nanoparticles for combined photothermal-chemotherapy.

Multifunctional hollow mesoporous silica nanoparticles were constructed by firstly loading with doxorubicin and then capping with disulfide linked ß-cyclodextrin followed by complexation with adamantane functionalized indocyanine dye, showing improved anticancer efficacy through combined photothermal-chemotherapy.

Theranostic Prodrug Vesicles for Imaging Guided Codelivery of Camptothecin and siRNA in Synergetic Cancer Therapy.

The construction of prodrugs has been a popular strategy to overcome the limitations of chemotherapeutic drugs. However, complicated synthesis procedures and laborious purification steps make the fabrication of amphiphilic prodrugs rather difficult. By harnessing the concept of host-guest interaction, we designed and prepared a supra-amphiphile consisting of a dendritic cyclodextrin host and an adamantane/naphthalimide-modified camptothecin guest through glutathione-responsive disulfide linkage. This host-guest complex could self-assemble in aqueous solution to give nanosized vesicles. When the disulfide bond in adamantane/naphthalimide-modified camptothecin was cleaved by glutathione, the fluorescence of the freed adamantane/naphthalimide unit showed a significant red shift with enhanced intensity. Such glutathione-responsive fluorescence change allows for intracellular imaging and simultaneous monitoring of drug release in real time. On account of abundant positively charged amine groups on the supramolecular vesicle surface, siRNA (siPlK1) could be efficiently loaded on the vesicle. The gel retardation and fluorescence experiments proved that the siPlK1 was successfully bonded to the supramolecular vesicle. The vesicle with dendritic cyclodextrin ring exhibited negligible cytotoxicity even at high concentrations, avoiding the shortcoming of cytotoxicity from commonly used gene vectors. In vitro studies demonstrated that the loaded siRNA was transported into cancer cells to improve cancer therapeutic efficacy. Thus, we developed a prodrug-based supramolecular amphiphile via the host-guest interaction with better therapeutic performance than free camptothecin. The assembled system was utilized as a drug/gene vector to achieve combinational gene therapy and chemotherapy with a synergistic effect, providing an alternative strategy to deliver both prodrug and therapeutic gene.

Redox and pH Dual Responsive Polymer Based Nanoparticles for In Vivo Drug Delivery.

Responsive nanomaterials have emerged as promising candidates as drug delivery vehicles in order to address biomedical diseases such as cancer. In this work, polymer-based responsive nanoparticles prepared by a supramolecular approach are loaded with doxorubicin (DOX) for the cancer therapy. The nanoparticles contain disulfide bonds within the polymer network, allowing the release of the DOX payload in a reducing environment within the endoplasm of cancer cells. In addition, the loaded drug can also be released under acidic environment. In vitro anticancer studies using redox and pH dual responsive nanoparticles show excellent performance in inducing cell death and apoptosis. Zebrafish larvae treated with DOX-loaded nanoparticles exhibit an improved viability as compared with the cases treated with free DOX by the end of a 3 d treatment. Confocal imaging is utilized to provide the daily assessment of tumor size on zebrafish larva models treated with DOX-loaded nanoparticles, presenting sustainable reduction of tumor. This work demonstrates the development of functional nanoparticles with dual responsive properties for both in vitro and in vivo drug delivery in the cancer therapy.

Anticancer Effect of α-Tocopheryl Succinate Delivered by Mitochondria-Targeted Mesoporous Silica Nanoparticles.

Mitochondria targeted mesoporous silica nanoparticles (MSNPs) having an average diameter of 68 nm were fabricated and then loaded with hydrophobic anticancer agent α-tocopheryl succinate (α-TOS). The property of targeting mitochondria was achieved by the surface functionalization of triphenylphosphonium (TPP) on MSNPs, since TPP is an effective mitochondria-targeting ligand. Intracellular uptake and mitochondria targeting of fabricated MSNPs were evaluated in HeLa and HepG2 cancerous cell lines as well as HEK293 normal cell line. In addition, various biological assays were conducted with the aim to investigate the effectiveness of α-TOS delivered by the functional MSNPs, including studies of cytotoxicity, mitochondria membrane potential, intracellular adenosine triphosphate (ATP) production, and apoptosis. On the basis of these experiments, high anticancer efficiency of α-TOS delivered by mitochondria targeted MSNPs was demonstrated, indicating a promising application potential of MSNP-based platform in mitochondria targeted delivery of anticancer agents.

Responsive Prodrug Self-Assembled Vesicles for Targeted Chemotherapy in Combination with Intracellular Imaging.

Targeted drug delivery systems having controlled drug release property with an inherent fluorescence reporter have drawn a lot of attention in nanomedicine. However, only very few prodrugs can be directly used to construct such delivery systems. Herein, we report that an amphiphilic chlorambucil-based prodrug consisting of a fluorescence reporter and a d-mannose targeting ligand could directly self-assemble into glutathione-responsive nanovesicles for selective cancer therapy and intracellular imaging. These nanovesicles could be dissociated to release the chlorambucil drug with obviously red-shifted fluorescence when internalized by d-mannose receptor-overexpressed MCF-7 cancer cells. In addition, the nanovesicles displayed better selectivity and higher therapy efficiency than free chlorambucil drug.

Incorporating a guanidine-modified cytosine base into triplex-forming PNAs for the recognition of a C-G pyrimidine-purine inversion site of an RNA duplex.

RNA duplex regions are often involved in tertiary interactions and protein binding and thus there is great potential in developing ligands that sequence-specifically bind to RNA duplexes. We have developed a convenient synthesis method for a modified peptide nucleic acid (PNA) monomer with a guanidine-modified 5-methyl cytosine base. We demonstrated by gel electrophoresis, fluorescence and thermal melting experiments that short PNAs incorporating the modified residue show high binding affinity and sequence specificity in the recognition of an RNA duplex containing an internal inverted Watson-Crick C-G base pair. Remarkably, the relatively short PNAs show no appreciable binding to DNA duplexes or single-stranded RNAs. The attached guanidine group stabilizes the base triple through hydrogen bonding with the G base in a C-G pair. Selective binding towards an RNA duplex over a single-stranded RNA can be rationalized by the fact that alkylation of the amine of a 5-methyl C base blocks the Watson-Crick edge. PNAs incorporating multiple guanidine-modified cytosine residues are able to enter HeLa cells without any transfection agent.

Photosensitizer anchored gold nanorods for targeted combinational photothermal and photodynamic therapy.

Silylated zinc phthalocyanine (ZnPc) was anchored onto silica-coated gold nanorods (AuNR) with retained local surface plasmon resonance (LSPR). Independent LSPR and singlet oxygen production of anchored ZnPc enhance the photothermal and photodynamic efficacy of the obtained AuNR-Si-ZnPc under NIR light excitation. AuNR-Si-ZnPc was further grafted with hyaluronic acid (HA). Since HA has selective targeting capability to CD44 antigens, the final hybrid could target cancer cells directly for synergistic photothermal and photodynamic therapy.

Polymeric Prodrug Grafted Hollow Mesoporous Silica Nanoparticles Encapsulating Near-Infrared Absorbing Dye for Potent Combined Photothermal-Chemotherapy.

In this study, polymeric prodrug coated hollow mesoporous silica nanoparticles (HMSNs) with encapsulated near-infrared (NIR) absorbing dye were prepared and explored for combined photothermal-chemotherapy. A copolymer integrated with tert-butoxycarbonyl protected hydrazide groups and oligoethylene glycols was initially grafted on the surface of HMSNs via reversible addition-fragmentation chain-transfer (RAFT) polymerization followed by the deprotection to reactivate the hydrazide groups for the conjugation of anticancer drug doxorubicin (DOX). DOX was covalently bound onto the polymer substrate by acid-labile hydrazone bond and released quickly in weak acidic environment for chemotherapy. The hollow cavity of HMSNs was loaded with an NIR absorbing dye IR825 to form the final multifunctional hybrid denoted as HMSNs-DOX/IR825. The hybrid exhibited good dispersity and stability as well as high light-to-heat conversion efficiency. As revealed by confocal microscopy and flow cytometry analysis, the hybrid was efficiently taken up by cancer cells, and the conjugated DOX could be released under the cellular environment. In vitro cytotoxicity study demonstrated that anticancer activity of HMSNs-DOX/IR825 could be significantly improved by the NIR irradiation, which led to a satisfactory therapeutic efficacy through the combination treatment. Thus, the developed hybrid could be a promising candidate for the combined photothermal-chemotherapy of cancer.

Host-Guest Interaction-Mediated Construction of Hydrogels and Nanovesicles for Drug Delivery.

Hand-in-hand or head-to-head: A novel naphthalimide derivative is successfully designed and synthesized, which can self-assemble to produce hydrogels. When injecting this compound into CB[8] solution, the nanovesicles are obtained with a narrow size distribution. The cytotoxicity assay confirms that doxorubicin-loaded nanocarriers show therapeutic effects to cancer cells.

Targeted delivery of doxorubicin to mitochondria using mesoporous silica nanoparticle nanocarriers.

A lot of investigations have been conducted using mesoporous silica nanoparticles (MSNPs) functionalized with different targeting ligands in order to deliver various hydrophobic and hydrophilic drugs to targeted cancer cells. However, the utilization of MSNPs to deliver drug molecules to targeted subcellular organelles has been rarely reported. In this work, we applied targeting ligand-conjugated MSNPs with an average diameter of 80 nm to deliver the anticancer drug doxorubicin (DOX) to mitochondria. Triphenoylphosphonium (TPP) was functionalized on MSNPs as a mitochondria targeting ligand. Mitochondria targeting efficiency was demonstrated in HeLa cells by a co-localization study of mitochondria and functionalized MSNPs as well as by fluorescence analysis in isolated mitochondria. In addition, enhanced cancer cell killing efficacy was achieved when using DOX-loaded and TPP-functionalized MSNPs for mitochondria-targeted delivery. Lowered adenosine triphosphate (ATP) production and decreased mitochondrial membrane potential were observed, demonstrating the mitochondria dysfunction caused by delivered DOX. The positive results indicate promising application potential of MSNPs in targeted subcellular drug delivery.

Imaging-Guided Drug Release from Glutathione-Responsive Supramolecular Porphysome Nanovesicles.

Drug delivery systems that can be employed to load anticancer drugs and release them triggered by a specific stimulus, such as glutathione, are of great importance in cancer therapy. In this study, supramolecular porphysome nanovesicles that were self-assembled by amphiphilic porphyrin derivatives were successfully constructed, mainly driven by the π-π stacking, hydrogen bonding, and hydrophobic interactions, and were used as carriers of anticancer drugs. The nanovesicles are monodispersed in shape and uniform in size. The drug loading and in vitro drug release investigations indicate that these nanovesicles are able to encapsulate doxorubicin (DOX) to achieve DOX-loaded nanovesicles, and the nanovesicles could particularly release the loaded drug triggered by a high concentration of glutathione (GSH). More importantly, the drug release in cancer cells could be monitored by fluorescent recovery of the porphyrin derivative. Cytotoxicity experiments show that the DOX-loaded nanovesicles possess comparable therapeutic effect to cancer cells as free DOX. This study presents a new strategy in the fabrication of versatile anticancer drug nanocarriers with stimuli-responsive properties. Thus, the porphysome nanovesicles demonstrated here might offer an opportunity to bridge the gap between intelligent drug delivery systems and imaging-guided drug release.

Polymer-Coated Hollow Mesoporous Silica Nanoparticles for Triple-Responsive Drug Delivery.

In this study, pH, reduction and light triple-responsive nanocarriers based on hollow mesoporous silica nanoparticles (HMSNs) modified with poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) were developed via surface-initiated atom transfer radical polymerization. Both reduction-cleavable disulfide bond and light-cleavable o-nitrobenzyl ester were used as the linkages between HMSNs and pH-sensitive PDEAEMA polymer caps. A series of characterization techniques were applied to characterize and confirm the structures of the intermediates and final nanocarriers. Doxorubicin (DOX) was easily encapsulated into the nanocarriers with a high loading capacity, and quickly released in response to the stimuli of reducing agent, acid environment or UV light irradiation. In addition, flow cytometry analysis, confocal laser scanning microscopy observations and cytotoxicity studies indicated that the nanocarriers were efficiently internalized by HeLa cancer cells, exhibiting (i) enhanced release of DOX into the cytoplasm under external UV light irradiation, (ii) better cytotoxicity against HeLa cells, and (iii) superior control over drug delivery and release. Thus, the triple-responsive nanocarriers present highly promising potentials as a drug delivery platform for cancer therapy.

Targeted delivery of 5-aminolevulinic acid by multifunctional hollow mesoporous silica nanoparticles for photodynamic skin cancer therapy.

5-Aminolevulinic acid (5-ALA) is a precursor of a strong photosensitizer, protoporphyrin IX (PphIX), for photodynamic therapy (PDT). Developing appropriate delivery carriers that can assist 5-ALA in bypassing the lipophilic barrier to directly enter into cancer cells is a research focus. The improved delivery of 5-ALA is even important for skin cancer therapy through PDT process. In this work, targeting ligand folic acid (FA)-functionalized hollow mesoporous silica nanoparticles (HMSNPs) were fabricated to deliver 5-ALA for PDT against B16F10 skin cancer cells. The FA targeting ligand enabled selective endocytosis of 5-ALA loaded HMSNPs into cancer cells. PphIX formed from delivered 5-ALA exhibited high photocytotoxicity to the cancer cells in vitro.

A preloaded amorphous calcium carbonate/doxorubicin@silica nanoreactor for pH-responsive delivery of an anticancer drug.

Biomedical applications of nontoxic amorphous calcium carbonate (ACC) nanoparticles have mainly been restricted because of their aqueous instability. To improve their stability in physiological environments while retaining their pH-responsiveness, a novel nanoreactor of ACC-doxorubicin (DOX)@silica was developed for drug delivery for use in cancer therapy. As a result of its rationally engineered structure, this nanoreactor maintains a low drug leakage in physiological and lysosomal/endosomal environments, and responds specifically to pH 6.5 to release the drug. This unique ACC-DOX@silica nanoreactor releases DOX precisely in the weakly acidic microenvironment of cancer cells and results in efficient cell death, thus showing its great potential as a desirable chemotherapeutic nanosystem for cancer therapy.

Intracellular delivery of antisense peptide nucleic acid by fluorescent mesoporous silica nanoparticles.

In order to overcome poor cell permeability of antisense peptide nucleic acid (PNA), a fluorescent mesoporous silica nanoparticle (MSNP) carrier was developed to successfully deliver antisense PNA into cancer cells for effective silence of B-cell lymphoma 2 (Bcl-2) protein expression in vitro. First, fluorescent MSNP functionalized with disulfide bond bridged groups was fabricated and characterized. Antisense and negative control PNAs were synthesized and further conjugated with fluorescent dye cyanine 5. Then, the PNAs were covalently connected with fluorescent MSNP via amidation between amino group of PNAs and carboxylic acid group on the MSNP surface. High intracellular concentration of glutathione serves as a natural reducing agent, which could cleave the disulfide bond to trigger the PNA release in vitro. Confocal laser scanning microscopy studies prove that PNA conjugated MSNP was endocytosed by HeLa cancer cells, and redox-controlled intracellular release of antisense PNA from fluorescent MSNP was successfully achieved. Finally, effective silencing of the Bcl-2 protein expression induced by the delivered antisense PNA into HeLa cells was confirmed by Western blot assay.

Photocontrolled nuclear-targeted drug delivery by single component photoresponsive fluorescent organic nanoparticles of acridin-9-methanol.

We report for the first time an organic nanoparticle based nuclear-targeted photoresponsive drug delivery system (DDS) for regulated anticancer drug release. Acridin-9-methanol fluorescent organic nanoparticles used in this DDS performed three important roles: (i) ″nuclear-targeted nanocarrier″ for drug delivery, (ii) ″phototrigger″ for regulated drug release, and (iii) fluorescent chromophore for cell imaging. In vitro biological studies reveal acridin-9-methanol nanoparticles of ~60 nm size to be very efficient in delivering the anticancer drug chlorambucil into the target nucleus, killing the cancer cells upon irradiation. Such targeted organic nanoparticles with good biocompatibility, cellular uptake property, and efficient photoregulated drug release ability will be of great benefit in the field of targeted intracellular controlled drug release.

Graphene oxide wrapped gold nanoparticles for intracellular Raman imaging and drug delivery.

Graphene oxide wrapped gold nanoparticles (Au@NGO) were fabricated by a one-step synthesis. The surface enhanced Raman scattering (SERS) signal from Au@NGO was employed for intracellular Raman imaging in HeLa cancer cells. Anticancer drug doxorubicin was attached onto the nanoparticle surface through noncovalent interactions, and was delivered into HeLa cells for chemotherapy.