Functionalized large pore mesoporous silica nanoparticles for gene delivery featuring controlled release and co-delivery

Novel mesoporous silica nanoparticles (LPMSNs) functionalised with degradable poly(2-dimethylaminoethyl acrylate) (PDMAEA) have been developed (PDMAEA–LPMSNs) as nano-carriers for gene delivery. The unique design of PDMAEA–LPMSNs has endowed this system with multiple functions derived from both the organic and inorganic moieties. The cationic polymer unit binds to genetic molecules and undergoes a self-catalyzed hydrolysis in water to form a non-toxic anionic polymer poly(acrylic acid), allowing controlled release of siRNA in the cells. The nanopores of the LPMSNs provide a reservoir for storage and release of chloroquine to facilitate endosomal escape. The PDMAEA–LPMSN composites were characterized by elemental analysis (EA), X-ray photoelectron spectroscopy (XPS), solid-state 13C magic-angle spinning nuclear magnetic resonance (MAS-NMR), thermogravimetric analysis (TGA), and nitrogen sorption techniques. Their siRNA delivery performance was tested in a KHOS cell line, showing promising potential for co-delivery of genes and drugs

Blood pressure percentiles and systemic hypertension-associated factors among children aged between 6 and 15 years in Southern Vietnam

Background: The present study determined blood pressure percentiles in children aged between 6 and 15 years in Southern Vietnam. Material and methods: Blood pressure was measured in a random sample of 1080 students aged 6–15 years who was studying at primary and secondary high schools in My Tho city, Vietnam. A descriptive cross-sectional study was conducted from November 2019 to June 2020. To diagnose children systemic hypertension, the blood pressure must be above the 95th percentile. Data were analyzed by IBM SPSS statistics software version 20.0. The Chi-squared test was employed to evaluate the relationship between systemic hypertension and child demographic characteristics including gender and obesity. Results: The results showed that the 95th percentiles of systolic and diastolic blood pressure of the children was 110/70 mm Hg in the 6-year-old group, 120/75 mm Hg in the 7 to12-year-old group and 125/80 mm Hg in the 13 to 15-year-old group, respectively. The rate of systemic hypertension in the children was 10% whereas boys had a 1.2 time higher risk of systemic hypertension than girls (p > 0.05). Obese children had an 8.6 time higher risk of systemic hypertension than non-obese ones (p < 0.001). Conclusion: The blood pressure percentile chart of school children aged 6–15 years were reported here for the first time in Vietnam. The results provided useful information in early diagnosis and timely treatment of systemic hypertension in children

Precise Control of Both Dispersity and Molecular Weight Distribution Shape by Polymer Blending

The breadth and the shape of molecular weight distributions can significantly influence fundamental polymer properties that are critical for various applications. However, current approaches require the extensive synthesis of multiple polymers, are limited in dispersity precision and are typically incapable of simultaneously controlling both the dispersity and the shape of molecular weight distributions. Here we report a simplified approach, whereby on mixing two polymers (one of high D and one of low D), any intermediate dispersity value can be obtained (e.g. from 1.08 to 1.84). Unrivalled precision is achieved, with dispersity values obtained to even the nearest 0.01 (e.g. 1.37 -> 1.38 -> 1.39 -> 1.40 -> 1.41 -> 1.42 -> 1.43 -> 1.44 -> 1.45), while maintaining fairly monomodal molecular weight distributions. This approach was also employed to control the shape of molecular weight distributions and to obtain diblock copolymers with high dispersity accuracy. The straightforward nature of our methodology alongside its compatibility with a wide range of polymerisation protocols (e.g. ATRP, RAFT), significantly expands the toolbox of tailored polymeric materials and makes them accessible to all researchers.ISSN:1433-7851ISSN:1521-3773ISSN:0570-083

Tailoring polymer dispersity by mixing ATRP initiators

Herein we present a simple batch method to control polymer dispersity using a mixture of two ATRP initiators with different reactivities. A wide dispersity spectrum (D similar to 1.1-1.7) is achieved by altering the ratio between the two ATRP initiators while sustaining fairly monomodal molecular weight distributions. Depending on the targeted dispersity, a distinct kinetic profile was observed and, in contrast to previous ATRP approaches, near-quantitative conversions were obtained even for the highest dispersities. High end-group fidelity was also maintained in all cases as exemplified by chain extensions. Significantly, this method can be applied to various ATRP protocols as well as to various monomer classes.ISSN:1759-9962ISSN:1759-995

Tuning Ligand Concentration in Cu(0)-RDRP: A Simple Approach to Control Polymer Dispersity

Cu(0)-reversible deactivation radical polymerization (RDRP) is a versatile polymerization tool, providing rapid access to well-defined polymers while utilizing mild reaction conditions and low catalyst loadings. However, thus far, this method has not been applied to tailor dispersity, a key parameter that determines the physical properties and applications of polymeric materials. Here, we report a simple to perform method, whereby Cu(0)-RDRP can systematically control polymer dispersity (Đ = 1.07–1.72), while maintaining monomodal molecular weight distributions. By varying the ligand concentration, we could effectively regulate the rates of initiation and deactivation, resulting in polymers of various dispersities. Importantly, both low and high dispersity PMA possess high end-group fidelity, as evidenced by MALDI-ToF-MS, allowing for a range of block copolymers to be prepared with different dispersity configurations. The scope of our method can also be extended to include inexpensive ligands (i.e., PMDETA), which also facilitated the polymerization of lower propagation rate constant monomers (i.e., styrene) and the in situ synthesis of block copolymers. This work significantly expands the toolbox of RDRP methods for tailoring dispersity in polymeric materials.ISSN:2694-245

Controlling size, shape, and charge of nanoparticles via low-energy miniemulsion and heterogeneous RAFT polymerization

Size, shape, and charge are key parameters of nanoparticles, and variations in these parameters can significantly impact their properties and applications. Among various nanoparticle synthesis methods, the combination of low-energy miniemulsions with reversible addition-fragmentation chain-transfer (RAFT) polymerization allows for the facile, rapid, and environmentally friendly preparation of uniform nanoparticles. However, this method cannot, yet, simultaneously control the size, shape, and charge of nanoparticles, thereby limiting its potential applications. Here we report the synthesis of polymeric nanoparticles with concurrent control over particle size, shape, and charge via low-energy miniemulsion and heterogeneous RAFT polymerization. Key to our approach is the combination of (i) a macromolecular surface-active agent to facilitate the formation of nanodroplets, (ii) various small-molecule surfactants with different charges to control the size and charge of nanodroplets, and (iii) a molecular transformer to control the morphology of the final polymeric nanoparticles. In particular, negatively charged polystyrene nanoparticles of different sizes (from ∼100 to ∼500 nm) and shapes (sphere, worm, and vesicle) were obtained by simply tuning the amount of added sodium dodecyl sulfate (SDS) and toluene. The nanoparticle charge was then switched from negative to positive by replacing SDS with cetyltrimethylammonium bromide (CTAB), a positively charged surfactant. In addition, biocompatible and neutral surfactants (including Tweens and Span 80) were employed to tune the nanoparticle size yielding challenging-to-synthesize nanoworms. This work provides a simple but powerful approach to produce nanoparticles of different properties, thus expanding the scope of nanomaterials made by RAFT low-energy miniemulsion polymerization.ISSN:0014-3057ISSN:1873-194

The effect of surface-active statistical copolymers in low-energy miniemulsion and RAFT polymerization

Low-energy miniemulsions enable the production of uniform nanodroplets for a wide range of applications without the need for using specialized equipment. However, low-energy miniemulsions are typically formed in the presence of a surface-active agent with a specific structure and property. In this work, we elucidate the role of a surface-active statistical copolymer, poly(N-(2-hydroxypropyl) methacrylamide-co-di(ethylene glycol) ethyl ether methacrylate) P(HPMA-co-DEGMA), in the formation of low-energy miniemulsions and reversible addition-fragmentation chain-transfer (RAFT) polymerization, enabling the design of a new series of surface-active statistical copolymers. In particular, we found that the HPMA/DEGMA ratio and copolymer molecular weight significantly affect the interfacial tension between water and styrene and as a result, the size of nanodroplets and the RAFT miniemulsion polymerization. Importantly, these findings allowed for the design and synthesis of novel surface-active statistical copolymers composed of DEGMA and various hydrophilic moieties that can also substantially lower the interfacial tension to below 12 mN m(-1). Furthermore, the new copolymer of DEGMA with methacrylamide (MAAm) resulted in the smallest nanodroplet size. This copolymer was subsequently selected to trigger the RAFT polymerization of styrene yielding nanoparticles of different morphologies including worm balls, worms, and vesicles. This work sheds light on the role of surface-active statistical copolymers and significantly expands the availability of surface-active agents for low-energy miniemulsion and RAFT polymerization.ISSN:1759-9962ISSN:1759-995

The thermodynamics and kinetics of depolymerization: what makes vinyl monomer regeneration feasible?

Depolymerization is potentially a highly advantageous method of recycling plastic waste which could move the world closer towards a truly circular polymer economy. However, depolymerization remains challenging for many polymers with all-carbon backbones. Fundamental understanding and consideration of both the kinetics and thermodynamics are essential in order to develop effective new depolymerization systems that could overcome this problem, as the feasibility of monomer generation can be drastically altered by tuning the reaction conditions. This perspective explores the underlying thermodynamics and kinetics governing radical depolymerization of addition polymers by revisiting pioneering work started in the mid-20th century and demonstrates its connection to exciting recent advances which report depolymerization reaching near-quantitative monomer regeneration at much lower temperatures than seen previously. Recent catalytic approaches to monomer regeneration are also explored, highlighting that this nascent chemistry could potentially revolutionize depolymerization-based polymer recycling in the future.ISSN:2041-6520ISSN:2041-653

Controlling polymer dispersity using switchable RAFT agents: Unravelling the effect of the organic content and degree of polymerization

Dispersity can significantly affect material properties and related applications and as such is a significant parameter to control in polymer design. Switchable RAFT agents were recently utilized as an efficient tool to tailor polymer dispersity. In this work, we investigate the effect of the organic solvent and targeted degree of polymerization (DP) in attaining dispersity-controlled homopolymers and block copolymers. By varying the addition of acid in pure aqueous media we found that a dispersity range between 1.16 and 1.58 could be obtained while the gradual incorporation of the organic content led to broader dispersity ranges. Pleasingly, when the polymerizations were performed in aqueous media, dispersity could be efficiently controlled regardless of the targeted degree of polymerization (from DP 50 to DP 800). Instead, in mixtures containing [DMF]:[H2O] = 4:1, dispersity could be successfully tailored only up to DP = 200 while for higher targeted DPs, a reduction in the final dispersity was not feasible. To expand the scope of our system, we subsequently exploited alternative organic solvents including DMAc, dioxane, DMSO, and ACN. While DMAc showed a side reaction attributed to the high amounts of acid employed, the other solvents successfully resulted in an efficient control over dispersity with ACN requiring the lowest amount of acid to achieve the lowest dispersity value (i.e. 2 equivalents of acid yielded D ~ 1.19). Notably, the highest D polymers synthesized in the various solvents displayed very high end group fidelity as characterized by mass-spectrometry and in-situ chain extensions. After establishing optimal reaction conditions, we also synthesized a range of exemplary diblock and triblock copolymers (with alternating low and high D) demonstrating excellent dispersity control upon subsequent block additions.ISSN:0014-3057ISSN:1873-194