查找使用阿拉丁产品的科研文献

ROS–Responsive Ferrocenyl Amphiphilic PAMAM Dendrimers for On–Demand Delivery of siRNA Therapeutics to Cancer Cells

Peng Chen,Zhihui Wang,Xinmo Wang,Junni Gong,Ju Sheng,Yufei Pan,Dandan Zhu,Xiaoxuan Liu

Small interfering RNA (siRNA) therapeutics, characterized by high specificity, potency, and durability, hold great promise in the treatment of cancer and other diseases. However, the clinic implementation of siRNA therapeutics critically depends on the safe and on–demand delivery of siRNA to the target cells. Here, we reported a family of ferrocenyl amphiphilic dendrimers (Fc-AmDs) for on–demand delivery of siRNA in response to the high ROS content in cancer cells. These dendrimers bear ROS–sensitive ferrocene moieties in the hydrophobic components and positively chargeable poly(amidoamine) dendrons as the hydrophilic entities, possessing favorable safety profiles and ROS responsive properties. One of these ferrocenyl amphiphilic dendrimers,Fc-C8-AmD 8A, outperforms in siRNA delivery, benefiting from its optimal balance of hydrophobicity and hydrophilicity. Its ROS feature facilitates specific and efficient disassembly of its complex with siRNA in ROS–rich cancer cells for effective siRNA delivery and gene silencing. Moreover,Fc-C8-AmD 8Aalso integrates the features and beneficial properties of both lipid and dendrimer vectors. Therefore, it represents a novel on–demand delivery system for cancer cell–specific siRNA delivery. This work opens new perspectives for designing self–assembly nanosystems for on–demand drug delivery.

Synthesis of PAMAM-g-PEG-g-DS-g-RB@IO towards dual-modal imaging in atherosclerosis

Qi Hu,Jia Wei,Chao Fang,Ya-Peng Li,Jing-Yuan Wang

This study aimed to synthesize a dual-modal magnetic resonance imaging (MRI)/fluorescence imaging (FLI) nanoprobe in order to detect atherosclerosis. Herein, we had prepared the polyamidoamine-graft-poly (ethylene glycol) (PAMAM-g-PEG) as the carrier. Dextran sulfate (DS) and Rhodamine B (RB) were grafted to PAMAM-g-PEG continuously through reductive amination and amidation reaction to synthesize PAMAM-g-PEG-g-DS-g-RB. The structure of PAMAM-g-PEG-g-DS-g-RB was characterized through nuclear magnetic resonance (1H-NMR) and Fourier transform infrared spectroscopy (FTIR). A new water-soluble superparamagnetic iron oxide nanoparticles (IONPs) has been synthesized through simple ligand exchange between the iron oxide nanaparticles and PAMAM-g-PEG-g-DS-g-RB. The analysis of transmission electron microscopy (TEM) indicated that micelles were well dispersed in water and had uniform sizes. The result of thermogravimetric analysis (TGA) proved that about 83% (mass fraction) polymers were coated on the surface of IONPs. The MRI in vitro evaluation demonstrated a high R2 value (130.8 mM−1s−1) to be served as a T2-weighted contrast agent. The cell counting kit (CCK) assay showed no significant toxicity in RAW264.7. The above results confirmed that PAMAM-g-PEG-g-DS-g-RB@IO could play an significant role of MRI and FLI in the atherosclerosis.

Dilution-Stable PAMAM G1-Grafted Polyrotaxane Supermolecules Deliver Gene into Cells through a Caveolae-Dependent Pathway

Huan Huang,Duanwen Cao,Linghao Qin,Shouqin Tian,Yang Liang,Shirong Pan,Min Feng

Numerous preclinical studies have demonstrated that polycation mediated gene delivery systems successfully achieved efficient gene transfer into cells and animal models. However, results of their clinical trials to date have been disappointing. That self-assembled gene and polycation systems should be stable undergoing dilution in the body is one of the prerequisites to ensuring efficiency of gene transfer in clinical trials, but it was neglected in most preclinical studies. In this account, we developed the dilution-stable PAMAM G1-grafted polyrotaxane (PPG1) supermolecules in which PAMAM G1-grafted α-cyclodextrins are threaded onto a PEG chain capped with hydrophobic adamantanamine. The PPG1/pDNA polyplex (approximate 100 nm in diameter) was very stable and kept its initial particle size and a uniform size distribution at ultrahigh dilution, whereas DNA/PEI 25K polyplex was above three times bigger at a 16-fold dilution than the initial size and their particle size distribution indicated multiple peaks mainly due to forming loose and noncompacted aggregates. PPG1 supermolecules showed significantly superior transfection efficiencies compared to either PEI 25K or Lipofectamine 2000 in most cell lines tested including normal cells (HEK293A) and cancer cells (Bel7402, HepG2, and HeLa). Furthermore, we found that the PPG1 supermolecules delivered DNA into HEK293A through a caveolae-dependent pathway but not a clathrin-dependent pathway as PEI 25K did. These findings raised the intriguing possibility that the caveolae-dependent pathway of PPG1 supermolecule/pDNA polyplex avoiding lysosomal degradation was attributed to their high transfection efficiency. The dilution-stable PPG1 supermolecule polyplex facilitating caveolae-dependent internalization has potential applications to surmount the challenges of high dilutions in the body and lysosomal degradation faced by most gene therapy clinical trials.

Polyamidoamine grafted with magnetic material (M-Gn-PAMAM): an efficient demulsifier for oil-contaminated industrial wastewater

Biao Long,Yu Ma,Ruixia Niu,Chuan Zhang,Hua Song,Hui Wang

A magnetic demulsifier, denoted M-Gn-PAMAM (n = 1, 2, 3), was synthesized by reacting polyamidoamine (PAMAM) dendrimers with Fe3O4@SiO2. The characteristics of magnetic nano-polymer were investigated via using XRD analysis, FT-IR, TEM, and VSM methods. The as-prepared M-Gn-PAMAM was highly effective at removing oil from wastewater produced from ASP flooding, with a maximum oil removal rate of 94% at 60 °C. Furthermore, the regeneration experiments illustrated that M-Gn-PAMAM could be readily recovered by an external magnetic field and it could be recycled up to 9 times without a significant loss in demulsification efficiency. In conclusion, the magnetic demulsifier synthesized in this study could be a promising nanomaterial for use in emulsified oil-water separation.

Increased Active Tumor Targeting by An αvβ3-Targeting and Cell-Penetrating Bifunctional Peptide-Mediated Dendrimer-Based Conjugate

Ma Pengkai,Yu Huajun,Zhang Xuemei,Mu Hongjie,Chu Yongchao,Ni Ling,Xing Pingping,Wang Yiyun,Sun Kaoxiang

Purpose A bifunctional RGDTAT peptide-modified PEG-PAMAM dendrimer conjugate RGDTAT-PEG-PAMAM (RTPP) was established for the targeted treatment of αvβ3-overexpressing tumor cells. Methods The RGDTAT peptide was synthesized and attached to PAMAM using PEG to construct the RTPP conjugate. The methotrexate (MTX) encapsulated RTPPM complex was prepared and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and in vitro release. The targeting ability was then studied in cells and tumor-bearing nude mice using fluorescence microscopy, confocal fluorescence microscopy, flow cytometry, and in vivo imaging. The cytotoxicity and pharmacokinetics of the RTPPM complex was also evaluated in cells and rats. Results The successful synthesis of the RTPP conjugate was confirmed by  1 H-NMR. DLS and TEM measurements revealed that the size was 37 nm and the complex had a spherical shape. RTPP and RTPPM were taken up by αvβ3-overexpressing cells more efficiently than by αvβ3-lowexpressing cells. The RTPP conjugate localized to the cell nucleus and accumulated in the tumor more efficiently than did the conjugates without RGDTAT. The pharmacokinetic study of the RTPPM complex showed sustained drug release. Conclusions The bifunctional peptide-mediated dendrimer-based RTPP conjugate can serve as a promising nanocarrier for targeted drug delivery to improve anti-tumor activity.

Multiwalled carbon nanotubes grafted with polyamidoamine (PAMAM) dendrimers and their influence on polystyrene supercritical carbon dioxide foaming

Jintao Yang,Linqi Huang,Yunguo Zhou,Feng Chen,Mingqiang Zhong

In this study, two types of multiwalled carbon nanotubes (MCNTs) are used for the preparation of polystyrene (PS)/MCNT composites. For each type of MCNT, two surface modifications, i.e., grafted with PS brushes (MCNTs-PS) and grafted with polyamidoamine (PAMAM) dendrimers and subsequent PS brushes (MCNTs-PAMAM-PS), are applied. The effects of aspect ratio and surface modification of the MCNTs on their dispersion in the PS matrix, as well as the dynamic mechanical properties and supercritical carbon dioxide (scCO 2 ) foaming of the composites, are investigated. The results indicate that the MCNTs-PS have a more uniform dispersion and a higher dynamic mechanical property reinforcement compared to MCNTs-NH 2 and MCNT S -PAMAM-PS. For the heterogeneous nucleation of MCNTs in PS scCO 2 microcellular foaming, long MCNTs show a small nucleation effect, while the nucleation effect of the short MCNTs is much more significant. Furthermore, the introduction of PAMAM dendrimers on the surface of MCNTs can improve the heterogeneous nucleation efficiency.

PAMAM generation-regulated chitosan/carboxymethyl cellulose–UiO-66-NH2 aerogels for CO2, formaldehyde, and cigarette-smoke purification

ZhenXiang Xu,Yuan Gao,JingLiang Wang,YunHuan Li,YiPeng Zhao,Xin Meng,Xia Feng,Li Chen,YiPing Zhao

Bio-based porous adsorbents for multicomponent air purification are often constrained by limited active-site density, insufficient control over hierarchical pore architectures, and inadequate mechanical robustness. Herein, chitosan was functionalized with poly(amidoamine) (PAMAM) dendrimers of different generations and combined with carboxymethyl cellulose (CMC) and UiO-66-NH 2 to construct nitrogen-enriched composite aerogels. The effects of PAMAM generation and UiO-66-NH 2 loading on the pore architecture, surface chemistry, mechanical response, and pollutant-capture performance of the aerogels were systematically evaluated. The optimized CG 2 MUNA-2 aerogel exhibited a well-connected porous network and sustained a compressive stress of 13.62 MPa at 80% strain. It achieved a CO 2 uptake of 0.64 mmol·g −1 at 273.15 K and a formaldehyde adsorption capacity of 1.57 mmol g −1 , while retaining 92.4% of its initial formaldehyde adsorption capacity after five adsorption-desorption cycles. When incorporated into cigarette filter rods, CG 2 MUNA-2 reduced CO, CO 2 , and total particulate matter by 30.87%, 14.01%, and 62.58%, respectively. Its superior overall performance was associated with a favorable balance among accessible amine functionalities, pore connectivity, and UiO-66-NH 2 dispersion. These results indicate that the coordinated regulation of PAMAM generation and MOF loading offers a rational materials-design strategy for developing biopolymer-based aerogels for multicomponent air-pollutant capture and cigarette-smoke purification. Download: Download high-res image (278KB) Download: Download full-size image

Development of biodegradable polymeric implants of RGD-modified PEG-PAMAM-DOX conjugates for long-term intratumoral release

Ke Wang,Xiaofeng Zhang,Lihong Zhang,Lili Qian,Chang Liu,Jiajun Zheng,Yanyan Jiang

Context: The sustained release implants can be directly implanted in tumor site by surgery and are promising for cancer treatment.Objective: RGD-modified PEGylated polyamidoamine (PAMAM) dendrimer with doxorubicin (DOX) conjugated by acid-sensitive linkage (RGD-PPCD) was a potential conjugate for tumor-targeted therapy. In order to enhance tumor retention ability and long-term effect of drug, we developed the DOX and its conjugate implants using poly(dl-lactic-co-glycolic acid) (PLGA), poly(dl-lactic acid) (PLA) and polyethylene glycol (PEG) as carrier materials.Methods: The implants were prepared by a simple solvent evaporation method. Different formulations with varying ratios of three polymers were designed, prepared and evaluated on the basis of viscosity, in vitro release and drying time. Furthermore, in vivo biodistribution and antitumor activity of the implants were studied in mice with subcutaneous C6 xenografts.Results: The optimized formulation was obtained with the 3:1 ratio of PLGA/PLA (w/w) and 1% PEG (wt.%). The drug release behavior of DOX, PPCD and RGD-PPCD implants prepared by the optimized formulation was similar according to the assessment of similarity factor f2, and the release curves were fell into three phases, including a lag-period, then the second phase which was consistent with zero-order model followed by a plateau. Data of total DOX remained in implants indicated the release were faster in vivo than in vitro. Moreover, intratumoral drug amount of RGD-PPCD implants was the highest 45 days after implantation. Correspondingly, the RGD-PPCD implants exhibited the strongest antitumor activity compared with PPCD and free DOX implants.Discussion and conclusion: This paper presents an exploratory research on macromolecule-drug conjugates, including RGD-PPCD and PPCD, which have the potential to be developed into long-term effect implants for tumor therapy with high efficiency and low systematic toxicity.

Cross-and-Capture: A Dual-Ligand PAMAM Nanocarrier for Sequential BBB Penetration and Ischemic Lesion Retention of Breviscapine

The clinical management of ischemic stroke is severely constrained by the blood–brain barrier (BBB), which restricts therapeutic drug access to the brain parenchyma, and the rapid systemic clearance of neuroprotective agents such as breviscapine (Bre). To overcome this dual challenge, we engineered a dual-targeting nanocarrier, L57&PGP-PEG-PAMAM, designed to sequentially traverse the BBB and anchor within the ischemic inflammatory microenvironment. This construct employs a PEGylated fifth-generation polyamidoamine (PAMAM) dendrimer scaffold functionalized with two distinct peptides: L57, which mediates transcytosis via LRP1 receptors on the BBB, and PGP, which targets CXCR2 receptors overexpressed on infiltrating neutrophils at the lesion. The resulting nano particles exhibited a hydrodynamic diameter of 140.2 ± 0.6 nm (zeta potential: 9.32 mV) and encapsulated Bre with a loading capacity of 20.12% and encapsulation efficiency of 71.78%, displaying sustained release (54.6% over 72 h). Crucially, in vivo fluorescence imaging confirmed markedly superior brain accumulation relative to non-targeted and PEGylated-only controls, while in a rat MCAO model, the formulation reduced infarct volume to 21.7 ± 6.4%, improved neurological scores to 1.52 ± 0.28, and suppressed pro-inflammatory IL-15/IL-27 levels—collectively outperforming free Bre. This work establishes a robust “cross-and-capture” strategy that effectively decouples BBB penetration from lesion-specific retention for ischemic stroke therapy.

A Sensitive Electrochemical Immunosensor Based on PAMAM Dendrimer-Encapsulated Au for Detection of Norfloxacin in Animal-Derived Foods

Bing Liu,Min Li,Yaoshuai Zhao,Mingfei Pan,Ying Gu,Wei Sheng,Guozhen Fang,Shuo Wang

In this work, a sensitive electrochemical immunosensor has been reported for the determination of norfloxacin in animal-derived foods. The poly (amidoamine) dendrimer encapsulated gold nanoparticles (PAMAM-Au) played dual roles in the proposed sensing platform which not only accelerated the electron transfer process of sensing, but also increased the efficiency of the immobilized antibody. The HRP-labeled antigen, as the signal labels in the immunosensor, was introduced to catalyze the following reaction of the substrate hydroquinone with the aid of H2O2in the competitive reaction. On the basis of the signal amplification of PAMAM-Au, the signal intensity was linearly related to the concentration of norfloxacin in the range of 1 μg·L−1–10 mg·L−1. All the results showed that the proposed strategy with low LOD (0.3837 μg·L−1) and favorable recovery (91.6–106.1%) in the practical sample, and it could provide a suitable protocol for norfloxacin detection in animal-derived foods with high sensitivity, good accuracy, and stability.Keywords:electrochemical immunosensor;dendrimer;signal amplification;norfloxacin;animal-derived foods

Electrochemical biosensors based on conducting polymer composite and PAMAM dendrimer for the ultrasensitive detection of acetamiprid in vegetables

Yan Zhou,Haitao Lü,Decheng Zhang,Keke Xu,Ni Hui,Jiasheng Wang

The cumulative harm caused by pesticide residues to environmental safety and human health is enormous, and the sensitive and selective detection pesticide in very trace amounts is currently a challenge. Herein, the biosensors for the ultrasensitive detection of acetamiprid (ACE) were proposed. The conducting polymer composite of phaseoloidin doped poly(3,4-ethyloxythiophene) (PL/PEDOT) was prepared with high surface area, excellent conductivity and stability, which was followed by the functionalization with poly(amidoamine) of the third generation (PAMAM). ACE aptamers were immobilized onto the platforms (PL/PEDOT and PAMAM/PL/PEDOT) for the development of ACE aptasensors. The concentration of ACE can be measured through both the increase of differential pulse voltammetry (DPV) signal change and the increase of the chronoamperometry (CA) signal change from the reduction of hydrogen peroxide catalyzed by PL/PEDOT. The ACE aptasensor based on PAMAM/PL/PEDOT exhibited linear ranges of 0.1 pg mL −1 -10 ng mL −1 and 0.1 fg-1.0 pg mL −1 , the detection limits as low as 0.0117 pg mL −1 and 0.0355 fg mL −1 (S/N = 3) through DPV and CA, respectively. Significantly, the response sensitivity of DNA/PAMAM/PL/PEDOT/GCE was 3.11 times higher than that of DNA/PL/PEDOT/GCE (by CA mode), proving that the PAMAM dendrimer can greatly enhance the sensing performance.

Fabrication of Fe3O4@polydopamine@polyamidoamine core–shell nanocomposites and their application for Cu(II) adsorption

Yukun Sun,Dongyun Li,Hui Yang,Xingzhong Guo

Fe3O4@polydopamine@polyamidoamine (Fe3O4@PDA@PAMAM) core–shell nanocomposites were successfully fabricated through a monodispersed Fe3O4 nanoflower synthesis, PDA modification and PAMAM grafting. The as-prepared single Fe3O4@PDA@PAMAM nanocomposite possesses a high relevant saturation magnetization (Ms) (30.25 emu g−1), while the coercivity (Hc) (10.85 Oe) and retentivity (Mr) (0.9062 emu g−1) were extremely low. The obtained Fe3O4@PDA@PAMAM has an adsorption capacity as high as 97.18 mg g−1 for Cu(II), and the adsorption process is in conformity with pseudo-second-order kinetics and the Langmuir isotherm model. Moreover, the effect of pH and thermodynamics of the adsorption process is also discussed briefly.