Inhibition of HIV-1 infection with curcumin conjugated PEG-citrate dendrimer; a new nano formulation.

BACKGROUND: Nano-drug delivery systems have become a promising approach to overcoming problems such as low solubility and cellular uptake of drugs. Along with various delivery devices, dendrimers are widely used through their unique features. PEG-citrate dendrimers are biocompatible and nontoxic, with the ability to improve drug solubility. Curcumin, a naturally occurring polyphenol, has multiple beneficial properties, such as antiviral activities. However, its optimum potential has been significantly hampered due to its poor water solubility, which leads to reduced bioavailability. So, the present study attempted to address this issue and investigate its antiviral effects against HIV-1. METHOD: The G2 PEG-citrate dendrimer was synthesized. Then, curcumin was conjugated to it directly. FTIR, HNMR, DLS, and LCMS characterized the structure of products. The conjugate displayed an intense yellow color. In addition, increased aqueous solubility and cell permeability of curcumin were achieved based on flow cytometry results. So, it could be a suitable vehicle for improving the therapeutic applications of curcumin. Moreover, cell toxicity was assessed using XTT method. Ultimately, the SCR HIV system provided an opportunity to evaluate the level of HIV-1 inhibition by the curcumin-dendrimer conjugate using a p24 HIV ELISA kit. RESULTS: The results demonstrated a 50% up to 90% inhibition of HIV proliferation at 12 µm and 60 µm, respectively. Inhibition of HIV-1 at concentrations much lower than CC50 (300 µM) indicates a high potential of curcumin-dendrimer conjugate against this virus. CONCLUSION: Thereby, curcumin-dendrimer conjugate proves to be a promising tool to use in HIV-1 therapy.

Dendrimer templated ionic liquid nanomagnetic for efficient coupling reactions.

In this research, a logical strategy with a recyclable synthetic perspective of view and a rational design to prepare a nanocatalyst with a dendrimer template containing ionic liquid is presented. Magnetic silica nanoparticles were prepared using the Stober method. Their surface was modified with the help of cyanuric chloride, melamine, and 1-methylimidazole as Linkers. Finally, the nanocatalyst was decorated with affordable copper metal. The dendrimer-templated nanocatalyst was identified by different analyses, such as FT-IR, SEM, TEM, XRD, EDX, TGA, CHN, and ICP-OES. Fe3O4@SiO2@NTMP-IL-Cu was used as a heterogeneous nanocatalyst with good performance and reusable in coupling syntheses. The synthesis of A3-coupling and Ullmann coupling was performed under solvent-free and THF conditions, respectively, with high yields. Reusability and high efficiency of products in the vicinity of this catalyst, the use of cheap and available metal are desirable features of this synthetic catalyst.

A Hydroxyquinoline Polymer with Excellent Amyloidosis Inhibition and Protein Delivery Ability to Combat Amyloid-ß-Mediated Neurotoxicity.

The accumulation of abnormal protein deposits known as amyloid-ß (Aß) plaques contributes to the development and progression of Alzheimer's disease. Aggregated Aß exacerbates oxidative stress by stimulating the production of reactive oxygen species (ROS) in a detrimental feedback loop. 8-Hydroxyquinoline (8-HQ) is recognized for its ability to inhibit or reverse Aß aggregation and reduce neurotoxicity. Here, an 8-HQ-based polymer, DHQ, was developed to combat Aß-mediated neurotoxicity by delivering an antioxidant enzyme. DHQ efficiently delivers superoxide dismutase into targeted cells, thereby downregulating the intracellular ROS level. Additionally, the polymer effectively inhibits the fibrillization of three proteins involved in fibrosis, ß-lactoglobulin (BLG), insulin, and Aß1-40, at nanomolar concentrations. Cell culture models demonstrated that DHQ reduces ROS levels induced by Aß1-40 aggregation, rescuing cell viability and preventing apoptosis. Intracellular delivery of SOD further enhanced the ability to maintain the ROS homeostasis. This polymer offers a multifaceted approach to treating diseases associated with amyloidosis.

Theoretical and Experimental Analyses of the Interfacial Mechanism of Dendrimer-Doxorubicin Complexes Formation.

The work presents correlations between the physicochemical properties of the carrier and the active substance and optimization of the conditions for creating an active system based on PAMAM dendrimers and doxorubicin. The study monitored the influence of the ionized form of the doxorubicin molecule on the efficiency of complex formation. The deprotonated form of doxorubicin occurs under basic conditions in the pH range of 9.0-10.0. In the presence of doxorubicin, changes in the zeta potential of the complex concerning the initial system are observed. These changes result from electrostatic interactions between the drug molecules and external functional groups. Based on changes in the absorbance intensity of UV-vis spectra, the binding of the drug in the polymer structure is observed depending on the pH of the environment and the molar ratio. Optimal conditions for forming complexes occur under alkaline conditions. UV-vis, Fourier transform infrared spectroscopy, and circular dichroism spectroscopy confirmed the stability of the formed dendrimer-DOX complex. Molecular dynamics simulations were conducted to gain a deeper insight into the molecular mechanism of DOX adsorption on and within the G4.0 PAMAM dendrimers. It was observed that the protonation state of both the dendrimer and DOX significantly influences the adsorption stability. The system exhibited high stability at high pH values (∼9-10), with DOX molecules strongly adsorbed on the dendrimer surface and partially within its bulk. However, under lower pH conditions, a reduction in adsorption strength was observed, leading to the detachment of DOX clusters from the dendrimer structure.

Endo-Encapsulated Multi-Resonance Dendrimers with Through-Space Interactions for Efficient Narrowband Blue-Emitting Solution-Processed OLEDs.

Different from conventional luminescent dendrimers with fluorophore tethered outside to dendron, here we first developed endo-encapsulated luminescent dendrimers with multi-resonance (MR) fluorophore embedded inside of carbazole dendrons by growing dendrons through 1,8-positions of central carbazole moiety to create a cavity for accommodating the fluorophore. This endo-encapsulated structure not only shields the fluorophore to fully resist aggregation-caused spectral broadening, but also induce through-space interactions between dendron and fluorophore via intramolecular π-stacking, giving lowered singlet state energy and reduced singlet-triplet energy splitting to accelerate reverse intersystem crossing (RISC) from triplet to singlet states. The resultant dendrimer containing 1,8-linked second-generation carbazole dendrons and boron, sulfur-doped polycyclic MR fluorophore exhibits narrowband blue emission at 471 nm with FWHM kept at 34 nm even in neat film, together with ~4 times enhancement of RISC rate constant compared to its exo-tethered counterpart. Solution-processed OLEDs based on the endo-encapsulated dendrimer reveal efficient narrowband blue emissions with maximum external quantum efficiency of 22.6%, representing the best device efficiency for blue-emitting multi-resonance dendrimers so far.

Antibiotic-Loaded Dendrimer Hydrogels in Periodontal Bone Regeneration: An In Vitro Release Feasibility Study.

The prescription of a course of oral antibiotics following bone grafting procedures is a common practice in clinical periodontics to reduce surgical site infections. The goal of this study is to characterize the release profile of antibiotics via local delivery using dendrimer hydrogels (DH) and to analyze the effect of two different particulate bone allografts on the release of the antibiotics in vitro. DH were synthesized from polyamidoamine (PAMAM) dendrimer G5 and polyethylene glycol diacrylate, and cefazolin was chosen as the antibiotic. The antibiotic-loaded samples were bathed in PBS and incubated at 37 °C; aliquots were taken (1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 12 h, 24 h, 48 h, 72 h) and analyzed using HPLC to determine the amounts of released cefazolin. In samples with DH, the estimated maximum concentration of cefazolin was 36.97 ± 2.39 µg/mL (95% CI: 34.58-39.36) with 50% released in 4.17 h (95%: 3.26-5.07) and an estimated growth rate of 0.27 (95% CI: 0.17-0.37). For samples without DH, the estimated maximum concentration of cefazolin was 167.4 ± 7.0 µg/mL (95% CI: 160.4-174.4) with 50% released in 2.36 h (95% CI: 2.05-2.67) and an estimated growth rate of 0.70 (95% CI: 0.54-0.87). We conclude that DH are a promising platform for sustained antibiotic release and that the presence of bone grafts did not significantly affect their release.

Halloysite functionalized with dendritic moiety containing vitamin B1 hydrochloride as a bio-based catalyst for the synthesis of 5-hydroxymthylfurfural.

Using halloysite clay and vitamin B1 hydrochloride, a novel acidic halloysite-dendrimer catalytic composite has been developed for conversion of fructose to 5-hydroxymthylfurfural. To grow the dendritic moiety on halloysite, it was first functionalized and then reacted with melamine, epichlorohydrin and vitamin B1 hydrochloride respectively. Then, the resulting composite was treated with ZnCl2 to furnish Lewis acid sites. Use of vitamin B1 as the cationic moiety of ionic liquid obviated use of toxic chemicals and resulted in more environmentally friendly composite. Similarly, dendritic moiety of generation 2 was also grafted on halloysite and the activity of both catalysts for conversion of fructose to 5-hydroxymthylfurfural was investigated to disclose the role of dendrimer generation. For the best catalytic composite, the reaction variables were optimized via RSM and it was revealed that use of 0.035 g catalyst per 0.1 g fructose at 95 °C furnished HMF in 96% yield in 105 min. Turnover numbers (TONs) and frequencies (TOFs) were estimated to be 10,130 and 5788 h-1, respectively. Kinetic studies also underlined that Ea was 22.85 kJ/mol. The thermodynamic parameters of Δ H ≠ , Δ S ≠ and Δ G ≠ , were calculated to be 23 kJ/mol, - 129.2 J/mol and 72.14 kJ/mol, respectively. Notably, the catalyst exhibited good recyclability and hot filtration approved heterogeneous nature of catalysis.

Polymers as Efficient Non-Viral Gene Delivery Vectors: The Role of the Chemical and Physical Architecture of Macromolecules.

Gene therapy is the technique of inserting foreign genetic elements into host cells to achieve a therapeutic effect. Although gene therapy was initially formulated as a potential remedy for specific genetic problems, it currently offers solutions for many diseases with varying inheritance patterns and acquired diseases. There are two major groups of vectors for gene therapy: viral vector gene therapy and non-viral vector gene therapy. This review examines the role of a macromolecule's chemical and physical architecture in non-viral gene delivery, including their design and synthesis. Polymers can boost circulation, improve delivery, and control cargo release through various methods. The prominent examples discussed include poly-L-lysine, polyethyleneimine, comb polymers, brush polymers, and star polymers, as well as hydrogels and natural polymers and their modifications. While significant progress has been made, challenges still exist in gene stabilization, targeting specificity, and cellular uptake. Overcoming cytotoxicity, improving delivery efficiency, and utilizing natural polymers and hybrid systems are vital factors for prospects. This comprehensive review provides an illuminating overview of the field, guiding the way toward innovative non-viral-based gene delivery solutions.

Astodrimer Sodium Nasal Spray versus Placebo in Non-Hospitalised Patients with COVID-19: A Randomised, Double-Blinded, Placebo-Controlled Trial.

BACKGROUND/OBJECTIVES: Dendrimer-based astodrimer sodium nasal spray was assessed for its ability to reduce SARS-CoV-2 load in outpatients with COVID-19, which remains a severe illness for vulnerable groups. METHODS: This was a randomised, double-blind, placebo-controlled clinical investigation evaluating the efficacy of astodrimer nasal spray in reducing SARS-CoV-2 viral burden in the nasopharynx of outpatients with COVID-19. Non-hospitalised adults with SARS-CoV-2 infection were randomised 1:1 to astodrimer or placebo four times daily from Day 1 to Day 7. Nasopharyngeal swabs for SARS-CoV-2 load determination were self-obtained daily from Day 1 to Day 8. The primary endpoint was an area under the curve of SARS-CoV-2 RNA copies/mL through Day 8 (vAUCd1-8). The primary analysis population was the modified intent-to-treat population (mITT: all randomised participants exposed to the study treatment who had at least one post-baseline viral load determination). Safety analyses included all randomised participants exposed to the study treatment. STUDY REGISTRATION: ISRCTN70449927; Results: 231 participants were recruited between 9 January and 20 September 2023. The safety population comprised 109 and 113 participants randomised to astodrimer and placebo, respectively, with 96 and 101 participants in the mITT. Astodrimer sodium nasal spray reduced the SARS-CoV-2 burden (vAUCd1-8) vs. placebo in non-hospitalised COVID-19 patients aged 16 years and over (-1.2 log10 copies/mL × Day). The reduction in SARS-CoV-2 load was statistically significant in those aged 45 years and older (-3.7, p = 0.017) and the effect increased in older age groups, including in those aged 65 years and older (-7.3, p = 0.005). Astodrimer sodium nasal spray increased the rate of viral clearance and helped alleviate some COVID-19 symptoms, especially loss of sense of smell. Overall, 31 participants (14%) had ≥1 adverse event (AE). Four AEs were deemed possibly related to treatment. Most AEs were of mild severity and occurred at similar rates in both treatment arms. CONCLUSIONS: Astodrimer nasal spray reduces viral burden and accelerates viral clearance, especially in older populations, and is well tolerated.

Triple-crosslinked double-network alginate/dextran/dendrimer hydrogel with tunable mechanical and adhesive properties: A potential candidate for sutureless keratoplasty.

An ideal adhesive hydrogel must possess high adhesion to the native tissue, biocompatibility, eligible biodegradability, and good mechanical compliance with the substrate tissues. We constructed an interpenetrating double-network hydrogel containing polysaccharides (alginate and dextran) and nanosized spherical dendrimer by both physical and chemical crosslinking, thus endowing the hydrogel with a broad range of mechanical properties, adhesive properties, and biological functions. The double-network hydrogel has moderate pore sizes and swelling properties. The chelation of calcium ions significantly enhances the tensile and compressive properties. The incorporation of dendrimer improves both the mechanical and adhesive properties. This multicomponent interpenetrating network hydrogel has excellent biocompatibility, tunable mechanical and adhesive properties, and satisfied multi-functions to meet the complex requirements of wound healing and tissue engineering. The hydrogel exhibits promising corneal adhesion capabilities in vitro, potentially supplanting the need for sutures in corneal stromal surgery and mitigating the risks associated with donor corneal damage and graft rejection during corneal transplantation. This novel polysaccharide and dendrimer hydrogel also shows good results in sutureless keratoplasty, with high efficiency and reliability. Based on the clinical requirements for tissue bonding and wound closure, the hydrogel provides insight into solving the mechanical properties and adhesive strength of tissue adhesives.

Systemically targeting monocytic myeloid-derived suppressor cells using dendrimers and their cell-level biodistribution kinetics.

The focus of nanoparticles in vivo trafficking has been mostly on their tissue-level biodistribution and clearance. Recent progress in the nanomedicine field suggests that the targeting of nanoparticles to immune cells can be used to modulate the immune response and enhance therapeutic delivery to the diseased tissue. In the presence of tumor lesions, monocytic-myeloid-derived suppressor cells (M-MDSCs) expand significantly in the bone marrow, egress into peripheral blood, and traffic to the solid tumor, where they help maintain an immuno-suppressive tumor microenvironment. In this study, we investigated the interaction between PAMAM dendrimers and M-MDSCs in two murine models of glioblastoma, by examining the cell-level biodistribution kinetics of the systemically injected dendrimers. We found that M-MDSCs in the tumor and lymphoid organs can efficiently endocytose hydroxyl dendrimers. Interestingly, the trafficking of M-MDSCs from the bone marrow to the tumor contributed to the deposition of hydroxyl dendrimers in the tumor. M-MDSCs showed different capacities of endocytosing dendrimers of different functionalities in vivo. This differential uptake was mediated by the unique serum proteins associated with each dendrimer surface functionality. The results of this study set up the framework for developing dendrimer-based immunotherapy to target M-MDSCs for cancer treatment.

A review on dendrimer-based nanoconjugates and their intracellular trafficking in cancer photodynamic therapy.

Nanotechnology-based cancer treatment has received considerable attention, and these treatments generally use drug-loaded nanoparticles (NPs) to target and destroy cancer cells. Nanotechnology combined with photodynamic therapy (PDT) has demonstrated positive outcomes in cancer therapy. Combining nanotechnology and PDT is effective in targeting metastatic cancer cells. Nanotechnology can also increase the effectiveness of PDT by targeting cells at a molecular level. Dendrimer-based nanoconjugates (DBNs) are highly stable and biocompatible, making them suitable for drug delivery applications. Moreover, the hyperbranched structures in DBNs have the capacity to load hydrophobic compounds, such as photosensitizers (PSs) and chemotherapy drugs, and deliver them efficiently to tumour cells. This review primarily focuses on DBNs and their potential applications in cancer treatment. We discuss the chemical design, mechanism of action, and targeting efficiency of DBNs in tumour metastasis, intracellular trafficking in cancer treatment, and DBNs' biocompatibility, biodegradability and clearance properties. Overall, this study will provide the most recent insights into the application of DBNs and PDT in cancer therapy.

DBNs' intracellular journey in cancer-PDT refines targeted therapy, boosting efficacy.DBN in PDT for tumour metastasis: targeting and drug release mechanisms.DBNs' biocompatibility, biodegradability and clearance were explored thoroughly.

Dendrimers as drug delivery systems for oncotherapy: Current status of promising applications.

Cancer affects millions of people worldwide, causing death and serious health problems. Despite significant investment in the development of new anticancer compounds, there are still several limitations that can still be found. Many compounds exhibit high levels of toxicity and low bioavailability. Therefore, it is urgent to design safer, more effective, and particularly more selective compounds for oncological treatment. Dendrimers are polymeric structures that have been shown to be potential drug nanocarriers to overcome physicochemical, pharmacokinetic, and indirect pharmacodynamic issues. Due to their versatility, they can be used in the design of nanovaccines, lipophilic complexes, amphiphilic complexes, smart nanocomplexes, and others. This work targets the use of dendrimers in oncological treatment and their importance and effectiveness as drug delivery systems for the development of new therapies. For this review, only publications from the last two years are considered in this review.

Discovery of a Novel Dual Targeting Peptide for Human Glioma: From In Silico Simulation to Acting as Targeting Ligand.

Purpose: Receptor-mediated transcytosis (RMT) is a more specific, highly efficient, and reliable approach to crossing the blood-brain-barrier (BBB) and releasing the therapeutic cargos into the brain parenchyma. Methods: Here, we introduced and characterized a human/mouse-specific novel leptin-derived peptide using in silico, in vitro and in vivo experiments. Results: Based on the bioinformatics analysis and molecular dynamics (MD) simulation, a 14 amino acid peptide sequence (LDP 14) was introduced and its interaction with leptin-receptor (ObR) was analyzed in comparison with an well known leptin-derived peptide, Lep 30. MD simulation data revealed a significant stable interaction between ligand binding domains (LBD) of ObR with LDP 14. Analyses demonstrated suitable cellular uptake of LDP 14 alone and its derivatives (LDP 14-modified G4 PAMAM dendrimer and LDP 14-modified G4 PAMAM/pEGFP-N1 plasmid complexes) via ObR, energy and species dependent manner (preferred uptake by human/mouse cell lines compared to rat cell line). Importantly, our findings illustrated that the entry of LDP 14-modified dendrimers in hBCEC-D3 cells not only is not affected by protein corona (PC) formation, as the main reason for diminishing the cellular uptake, but also PC per se can enhance uptake rate. Finally, fluorescein labeled LDP 14-modified G4 PAMAM dendrimers efficiently accumulated in the mice brain with lower biodistribution in other organs, in our in vivo study. Conclusion: LDP 14 introduced as a novel and highly efficient ligand, which can be used for drugs/genes delivery to brain tissue in different central nervous system (CNS) disorders.

Fluorinated PAMAM-Arginine Carrier Prodrugs for pH-Sensitive Sustained Ibuprofen Delivery.

OBJECTIVE: The development of an efficient, multifunctional drug delivery system overcoming different obstacles generally associated with drug formulations, including the poor accumulation of the active principle in the target site and its sustained release for prolonged time. METHODS: Our study proposes the development of a fluorinated poly(amidoamine) (PAMAM) carrier prodrug combining drug release boosted in alkaline environments with a possible implementation in 19F MRI applications. In particular, we functionalized the terminal primary amines of PAMAM G2 and G4 through an ad hoc designed fluorinated ibuprofen-arginine Michael acceptor to obtain multifunctional ibuprofen-PAMAM-Arg conjugates. RESULTS: These carriers demonstrated pH-dependent and sustained ibuprofen release for more than 5 days. This advantage was observed in both weak alkaline and physiological buffer solutions, allowing to overcome the limits associated to the burst release from similar fluorinated Arg-PAMAM dendrimers with ibuprofen physically encapsulated. CONCLUSION: These findings, coupled to the high biocompatibility of the system, suggest a potential synergistic biomedical application of our conjugates, serving as vehicles for drug delivery and as 19F magnetic resonance imaging contrast agents.

Hybrid Dendrimer Network based on Silsesquioxane and Glycidyl Methacrylate for Enhanced Adsorption of Iodine and Dyes in Environmental Remediation.

A novel hybrid network was synthesized in two steps: the first step involved the attachment of glycidyl methacrylate (GMA) to octa(aminophenyl) silsesquioxane (OAPS) through a ring-opening reaction, forming a hybrid dendrimer structure, and the second step involved the cross-linking of hybrid dendrimer using an azobisisobutyronitrile initiator to create the final hybrid network of OAPS-GMA. The synthesized hybrid material was comprehensively characterized using fourier transform infrared Spectroscopy (FTIR), nuclear magnetic resonance ((1H, 13C, and 29Si NMR) spectroscopy, thermogravimetric Analysis (TGA), and scanning electron microscopy (SEM). The BET surface area was found to be 25.44 m2/g, and significant 2.341 cm3/g of total pore volume was observed. The TGA analysis shows that the material is highly stable up to 450 °C. The synthesized network demonstrated remarkable adsorption capacities for iodine and dyes. It exhibited an iodine adsorption capacity of 3.4 g/g from vapors and 874 mg/g from solution. Additionally, it showed significant adsorption capacities for Rhodamine B and Congo red, with values of 762 mg/g and 517 mg/g, respectively. This study not only provides a novel method for preparing GMA-functionalized silsesquioxane-based porous hybrid polymers but also contributes to advancing solutions for environmental pollution issues.

Dendrimer Platforms for Targeted Doxorubicin Delivery-Physicochemical Properties in Context of Biological Responses.

The unique structure of G4.0 PAMAM dendrimers allows a drug to be enclosed in internal spaces or immobilized on the surface. In the conducted research, the conditions for the formation of the active G4.0 PAMAM complex with doxorubicin hydrochloride (DOX) were optimized. The physicochemical properties of the system were monitored using dynamic light scattering (DLS), circular dichroism (CD), and fluorescence spectroscopy. The Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) method was chosen to determine the preferential conditions for the complex formation. The highest binding efficiency of the drug to the cationic dendrimer was observed under basic conditions when the DOX molecule was deprotonated. The decrease in the zeta potential of the complex confirms that DOX immobilizes through electrostatic interaction with the carrier's surface amine groups. The binding constants were determined from the fluorescence quenching of the DOX molecule in the presence of G4.0 PAMAM. The two-fold way of binding doxorubicin in the structure of dendrimers was visible in the Isothermal calorimetry (ITC) isotherm. Fluorescence spectra and release curves identified the reversible binding of DOX to the nanocarrier. Among the selected cancer cells, the most promising anticancer activity of the G4.0-DOX complex was observed in A375 malignant melanoma cells. Moreover, the preferred intracellular location of the complexes concerning the free drug was found, which is essential from a therapeutic point of view.

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

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 8A also 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.

Analytical Model to Deduce the Conformational and Dynamical Behavior in Dendrimers: A Review.

This review utilizes an optimized Rouse-Zimm discrete hydrodynamic model and the preaveraged Oseen tensor, which accurately consider hydrodynamic interactions to study model dendrimers. We report the analytical theories that have been previously developed for the creation of generalized analytical models for dendrimers. These generalized theories were used to assess the conformational and dynamical behavior of the dendrimers. By including stiffness in the bonds, the neglect of excluded volume interactions may be somewhat offset. This is true at least in the case of short spacers. While the topological limitations on the directions and orientations of the individual bond vectors in dendrimers implement semiflexibility, the intensity of these contacts was determined by the potential geometric orientations of the bonds, and later on the excluded volume interactions in dendrimers, which were described in terms of the effective co-volume between nearest non-bonded monomers and modeled using the delta function pseudopotential. With the aid of the models developed, the authors condensed various conformational and dynamic properties of dendrimers that depend on their degree of semiflexibility and the strength of the excluded volume. These analyses came to the conclusion that the flexible dendrimer in one limit and the earlier described freely rotating model of dendrimers in the other constitute a highly generalized way of capturing a wide range of conformations in the developed mathematical model in dendrimers.

Ion-Selective Transport Promotion Enabled by Angstrom-Scale Nanochannels in Dendrimer-Assembled Polyamide Nanofilm for Efficient Electrodialysis.

The ion permeability and selectivity of membranes are crucial in nanofluidic behavior, impacting industries ranging from traditional to advanced manufacturing. Herein, we demonstrate the engineering of ion-conductive membranes featuring angstrom-scale ion-transport channels by introducing ionic polyamidoamine (PAMAM) dendrimers for ion separation. The exterior quaternary ammonium-rich structure contributes to significant electrostatic charge exclusion due to enhanced local charge density; the interior protoplasmic channels of PAMAM dendrimer are assembled to provide additional degrees of free volume. This facilitates the monovalent ion transfer while maintaining continuity and efficient ion screening. The dendrimer-assembled hybrid membrane achieves high monovalent ion permeance of 2.81 mol m-2 h-1 (K+), reaching excellent mono/multivalent selectivity up to 20.1 (K+/Mg2+) and surpassing the permselectivities of state-of-the-art membranes. Both experimental results and simulating calculations suggest that the impressive ion selectivity arises from the significant disparity in transport energy barrier between mono/multivalent ions, induced by the "exterior-interior" synergistic effects of bifunctional membrane channels.