Fluorinated dendrimer-mediated miR-30a delivery regulates the inflammation of macrophages and mitigates the symptoms of rheumatoid arthritis.

Abnormal expression of microRNAs (miRNAs) plays a significant role in the pathogenesis of rheumatoid arthritis (RA), and thus miRNA-based therapy has emerged as a promising approach for the RA treatment. Herein, miR-30a was successfully screened and identified to be an essential mediator for the inflammation of RA. MiR-30a could directly target the Snai1 gene and further regulate the Cad11 expression to inhibit the NF-κB and MAPK signaling pathways, contributing to the anti-inflammatory effect.

Ribonuclease A-polymer conjugates growth for cancer treatment.

Efficient delivery of therapeutic proteins is a critical aspect for protein-based cancer treatment. Herein, an growth approach was employed to prepare ribonuclease A (RNase A)-polymer conjugates by incorporating a cationic polymer, poly(,'-dimethylamino-2-ethyl methacrylate) (P(DMAEMA)), and a hydrophobic polymer, poly(-isopropylacrylamide) (P(NIPAM)), through atom transfer radical polymerization (ATRP). The synthesized RNase A-polymer conjugates (namely R-P(D--N)) could preserve the integrity of RNase A and exhibit a unique combination of cationic and hydrophobic properties, leading to enhanced intracellular delivery efficiency.

Fluorinated polyamidoamine dendrimer-mediated miR-23b delivery for the treatment of experimental rheumatoid arthritis in rats.

In rheumatoid arthritis (RA), insufficient apoptosis of macrophages and excessive generation of pro-inflammatory cytokines are intimately connected, accelerating the development of disease. Here, a fluorinated polyamidoamine dendrimer (FP) is used to deliver miR-23b to reduce inflammation by triggering the apoptosis of as well as inhibiting the inflammatory response in macrophages. Following the intravenous injection of FP/miR-23b nanoparticles in experimental RA models, the nanoparticles show therapeutic efficacy with inhibition of inflammatory response, reduced bone and cartilage erosion, suppression of synoviocyte infiltration and the recovery of mobility.

Superoxide dismutase-embedded metal-organic frameworks biomimetic mineralization for the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by chronic and spontaneous inflammation in the gastrointestinal tract, and has been associated with an improved level of reactive oxygen species (ROS). Herein, superoxide dismutase (SOD) was encapsulated into zeolitic imidazolate framework-zni (ZIF-zni) to construct a nanocomposite termed SOD@ZIF-zni through biomimetic mineralization, which was then used as a formulation for the IBD treatment. The SOD@ZIF-zni composite could efficiently suppress the level of ROS and pro-inflammatory cytokines, using the colorectal cancer cell line SW480 as a model.

Lipoic Acid-Modified Oligoethyleneimine-Mediated miR-34a Delivery to Achieve the Anti-Tumor Efficacy.

MiR-34a, an important tumor suppressor, has been demonstrated to possess great potential in tumor gene therapy. To achieve the upregulation of miR-34a expression level, an oligoethyleneimine (OEI) derivative was constructed and employed as the carrier through the modification with lipoic acid (LA), namely LA-OEI. In contrast to OEI, the derivative LA-OEI exhibited superior transfection efficiency measured by confocal laser scanning microscopy and flow cytometry, owing to rapid cargo release in the disulfide bond-based reduction sensitive pattern.

Urate oxidase loaded in PCN-222(Fe) with peroxidase-like activity for colorimetric detection of uric acid.

In the past two decades, the number of reports on the construction of uric acid (UA) sensors has increased dramatically, as it is a vital factor in the diagnosis of physiological functions and diseases. Among these sensors, cascade colorimetric detection based on peroxidase mimics has received great attention owing to the advantages of easier operation and more intuitive results. Herein, we report a simple UA detection method via the integration of urate oxidase (UOx) and PCN-222(Fe) with peroxidase-like activity, in which UOx is immobilized in PCN-222(Fe) by physical adsorption.

Dual ATP/reduction-responsive polyplex to achieve the co-delivery of doxorubicin and miR-23b for the cancer treatment.

Combination therapy based on the co-delivery of therapeutic genes and anti-cancer drugs has emerged as a promising approach in the cancer treatment, and stimuli-responsive delivery systems could further improve the therapeutic efficacy. Herein, an ATP aptamer and its complementary DNA were used to form Duplex into which doxorubicin (DOX) was loaded to construct DOX-Duplex, and then the lipoic acid-modified oligoethyleneimine (LA-OEI) was employed as a carrier to realize the co-delivery of DOX-Duplex and miR-23b. The ternary nanocomplex LA-OEI/miR-23b/DOX-Duplex showed excellent anti-proliferative effect by inducing the cell apoptosis via mitochondrial signaling pathway and arresting the cell cycle at S phase.

Artesunate-loaded porous PLGA microsphere as a pulmonary delivery system for the treatment of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) has emerged to be a significant cause of cancer mortality worldwide. Artesunate (ART) extracted from Chinese herb Artemisia annua L, has been proven to possess desirable anti-cancer efficacy, especially for the metastatic NSCLC treatment. Moreover, the poly(lactic-co-glycolic acid) (PLGA) microsphere has been considered to be a potential pulmonary delivery system for the sustained drug release to enhance the therapeutic efficacy of lung cancer.

Study the lipidoid nanoparticle mediated genome editing protein delivery using 3D intestinal tissue model.

Lipid nanoparticles are promising carriers for oral drug delivery. For bioactive cargos with intracellular targets, e.g.

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment.

Background: Multidrug resistance (MDR) has emerged to be a major hindrance in cancer therapy, which contributes to the reduced sensitivity of cancer cells toward chemotherapeutic drugs mainly owing to the over-expression of drug efflux transporters. The combination of gene therapy and chemotherapy has been considered as a potential approach to improve the anti-cancer efficacy by reversing the MDR effect.

Materials And Methods: The AS1411 aptamer-functionalized micelles were constructed through an emulsion/solvent evaporation strategy for the simultaneous co-delivery of doxorubicin and miR-519c.

Fluoropolymer-Mediated Intracellular Delivery of miR-23b for the Osteocyte Differentiation in Osteoblasts.

Emerging evidence suggests that microRNAs (miRNAs) play key roles in the regulation of multiple biological processes, including the differentiation of osteoblasts. Although miRNA-based gene therapy holds immense potential in the treatment of a variety of diseases, the intracellular delivery of miRNA remains challenging owing to the lack of efficient and safe gene carriers. In this study, a fluoropolymer (FP) is constructed through the modification of polyamidoamine (PAMAM) using heptafluorobutyric anhydride and then is used as a carrier for miR-23b transfection to induce osteocyte differentiation of osteoblasts.

and Study of Amphotericin B Formulation with Quaternized Bioreducible Lipidoids.

Invasive fungal infections are well-known causes of morbidity and mortality in immunocompromised patients. Amphotericin B (AmB) is a polyene fungicidal agent with excellent properties of the broad antifungal spectrum, high activity, and relatively rare drug resistance. However, significant toxicities limit the clinical application of AmB and its conventional formulation AmB deoxycholate (Fungizone).

A genipin-crosslinked protein-polymer hybrid system for the intracellular delivery of ribonuclease A.

Background: Therapeutic proteins have been widely used in the treatment of various diseases, and effective carriers are highly required for achieving protein delivery to obtain favorable treatment potency.

Materials And Methods: A protein-polymer hybrid system was constructed through the genipin-mediated crosslinking of polyethyleneimine with a weight-average molecular weight of 25,000 g/mol (PEI25K) and ribonuclease A (RNase A), namely RGP.

Results: The RGP nanoparticles were observed to be easily internationalized in HeLa cells owing to the introduction of positively charged PEI25K, thereby triggering the antiproliferative effects by cleaving RNA molecules in the tumor cells.

Inhibition of proliferation and migration of tumor cells through phenylboronic acid-functionalized polyamidoamine-mediated delivery of a therapeutic DNAzyme Dz13.

Background: The phenylboronic acid-functionalized polyamidoamine (PP) was employed as a gene carrier for Dz13 delivery, inducing an obvious anticancer response.

Materials And Methods: The Dz13 condensation ability of PP was evaluated through gel retardation assay. The cellular uptake mechanism of PP/Dz13 nanoparticles was studied using confocal laser scanning microscope and flow cytometer.

Phenylboronic acid-modified polyamidoamine-mediated delivery of short GC rich DNA for hepatocarcinoma gene therapy.

Phenylboronic acid was introduced on the surface of polyamidoamine to construct a derivative PP, which was further used as a tumor-targeting carrier for realizing the delivery of short GC rich DNA (GCD). The PP-mediated GCD delivery could disrupt the polymerization of microtubules and thus trigger a strong anti-proliferative effect through the induction of cell apoptosis and cell cycle arrest, using hepatocellular carcinoma cell line HepG2 as a model. In addition, the transfection of PP/GCD nanoparticles could efficiently suppress cell migration and invasion.

Phenylboronic acid-functionalized polyamidoamine-mediated miR-34a delivery for the treatment of gastric cancer.

In the present research, a tumor-targeted gene carrier, PPP, was constructed through the modification of phenylboronic acid onto the surface of a polyamidoamine dendrimer, and then miR-34a delivery was employed as a model to evaluate its anti-tumor efficacy. The carrier PPP was identified to possess favorable miR-34a binding and condensation ability and meanwhile protect miR-34a against nuclease degradation. Through confocal laser scanning microscopy and flow cytometry analysis, PPP-mediated cellular uptake of miR-34a was found to proceed through a sialic acid-dependent endocytosis pathway and the nanoparticles could achieve endosome/lysosome escape within 6 h.

A comprehensive review on histone-mediated transfection for gene therapy.

Histone has been considered to be an effective carrier in non-viral gene delivery due to its unique properties such as efficient DNA binding ability, direct translocation to cytoplasm and favorable nuclear localization ability. Meanwhile, the rapid development of genetic engineering techniques could facilitate the construction of multifunctional fusion proteins based on histone molecules to further improve the transfection efficiency. Remarkably, histone has been demonstrated to achieve gene transfection in a synergistic manner with cationic polymers, affording to a significant improvement of transfection efficiency.

Inhibition of cell proliferation and migration through nucleobase-modified polyamidoamine-mediated p53 delivery.

Introduction: The nucleobase 2-amino-6-chloropurine-modified polyamidoamine (AP-PAMAM) was used as a carrier for gene delivery to achieve the antitumor effects.

Methods And Materials: The condensation of plasmid was studied through gel retardation assay, and the transfection efficiency was evaluated through the transfection assay of pEGFP-N3 and pGL-3 plasmids. Using human cervical carcinoma cell line HeLa as a model, the inhibition of cell proliferation and migration was studied through flow cytometry, wound healing and Transwell migration assays, respectively.

Lipase-inorganic hybrid nanoflower constructed through biomimetic mineralization: A new support for biodiesel synthesis.

We reported a facile, economic and green method based on biomimetic mineralization to acquire lipase-inorganic hybrid nanoflower, which was then employed as a biocatalyst for biodiesel production. In the hybrid nanoflower, enzyme molecules and Cu ions were utilized as the organic and inorganic components, respectively. The morphology of nanoflower and the distribution and loading of proteins were systematically characterized by scanning electron microscopy, confocal laser scanning microscopy and ultraviolet-visible spectroscopy, which indicated the successful encapsulation of lipase in the hybrid nanoflower.

Nucleobase-modified polyamidoamine-mediated miR-23b delivery to inhibit the proliferation and migration of lung cancer.

The nucleobase analogue 2-amino-6-chloropurine was modified on the surface of polyamidoamine (PAMAM) to construct a derivative AP-PAMAM, and then it was used as a gene carrier for miR-23b delivery to achieve the anti-tumor effects. The carrier AP-PAMAM could condense miR-23b into stable nanoparticles with a particle size of 97.3 nm (N/P ratio of 50), which was favorable for the cellular uptake of nanoparticles.

Phenol degradation catalyzed by a peroxidase mimic constructed through the grafting of heme onto metal-organic frameworks.

The aim of this work was to construct a peroxidase mimic for achieving the phenol degradation through Fenton reaction. The enzyme mimic was synthesized through the conjugation of heme with the amino group of 2-amino-1,4-benzene dicarboxylate in UiO-66-NH (ZrMOF), namely Heme-ZrMOF. Compared to free heme, the composite Heme-ZrMOF exhibited an obviously enhanced ability for phenol degradation with up to 97.

Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA.

Herein, DNA duplex was constructed through the hybridization of adenosine triphosphate (ATP)-responsive aptamer and its cDNA in which GC-rich motif could be used to load doxorubicin (DOX), and then, cationic polymer PEI25K was used as a carrier to simultaneously condense DOX-Duplex and Bcl-2 siRNA to prepare the ternary nanocomplex polyethylenimine (PEI)/DOX-Duplex/siRNA. The ATP concentration gradient between the cytosol and extracellular environment could achieve the stable loading of DOX in duplex and the rapid drug release in an ATP-responsive manner. Using human prostate tumor cell line PC-3 as a model, an obvious induction of cell proliferation could be detected with a cell viability of 53.

Deuterohemin-Peptide Enzyme Mimic-Embedded Metal-Organic Frameworks through Biomimetic Mineralization with Efficient ATRP Catalytic Activity.

An enzyme mimic harboring iron porphyrin (DhHP-6) embedded in zeolite imidazolate framework-8 (ZIF-8) was constructed through a biomimetic mineralization approach to obtain composite DhHP-6@ZIF-8. The composite was then used as a catalyst in the atom transfer radical polymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate (PEGMA) in which poly(PEGMA) could be synthesized with monomer conversion of 76.1% and M of 45 900 g/mol, stronger than that obtained when using free DhHP-6 as a catalyst.

An ATP-Responsive Codelivery System of Doxorubicin and MiR-34a To Synergistically Inhibit Cell Proliferation and Migration.

Establishing stimulus-responsive nanosystems for the codelivery of anticancer drug and oligonucleotide is a promising strategy in cancer treatment owing to the combination of chemotherapy and gene therapy in a synergistic manner. Herein, an ATP aptamer and its cDNA sequence were first hybridized to produce the duplex, into which chemotherapeutic agent doxorubicin (DOX) interacted through the GC-rich motif of duplex, and PEI25K was then employed as a carrier to condense the DOX-loading duplex and miR-34a to construct the ternary nanocomplex PEI/DOX-Duplex/miR-34a. The nanocomplex exhibited a favorable drug release profile through the response to high concentration of ATP in the cytosol.

Chemoenzymatic Synthesis of Cholesterol--Poly(amine--ester) Amphiphilic Copolymer as a Carrier for miR-23b Delivery.

The lipase-catalyzed polymerization of -methyldiethanolamine, diethyl sebacate and ω-pentadecanolide was performed to construct a cationic poly(amine--ester), and a hydrophobic -(2-bromoethyl)carbamoyl cholesterol was then grafted onto its main chain through a quaternization reaction to prepare the amphiphilic copolymer Chol--PMSC-PPDL. The copolymer efficiently bound and condensed miR-23b to form stable nanocomplexes, which showed favorable cellular uptake and miR-23b transfection efficacy due to the introduction of the hydrophobic segment. After miR-23b delivery, an obvious inhibition of cell proliferation could be induced, which was attributed to the induction of cell apoptosis and cell cycle arrest.