Enhanced Photocatalytic Activity of V2C MXene-Coupled ZnO Porous Nanosheets with Increased Surface Area and Effective Charge Transfer.

Photocatalysis performs excellently when degrading organic pollutants, but the photocatalytic degradation rate is not high for most photocatalysts due to their narrow sunlight adsorption range and high recombination rate of electron hole pairs. Herein, we use V2C-MXene with a wide sunlight adsorption range to couple ZnO porous nanosheets and form ZnO/MXene hybrids using a facile electrostatic self-assembly method. The ZnO/MXene hybrids acquired demonstrated improved photochemical efficiency in breaking down methylene blue (MB) when contrasted with porous ZnO nanosheets. The degradation rate of MB reached 99.8% under UV irradiation for 120 min after the ZnO/MXene hybrid formation, while 38.6% was attained by the ZnO porous nanosheets. Moreover, photodegradation rate constants (k) were calculated as 3.05 × 10-3 and 5.42 × 10-2 min-1 for ZnO porous nanosheets and ZnO/MXene hybrids, respectively, indicating that the photodegradation performance was enhanced by 17.8 times after the modification of V2C. This was probably because the modification of V2C can increase the specific surface area to provide more sites for MB adsorption, widen the sunlight adsorption range to produce good photothermal effect, and facilitate the transfer of photogenerated carriers in ZnO to promote the reaction of more photogenerated carriers with MB. Hence, this work offers a simple approach to creating effective photocatalysts for breaking down organic contaminants.

Facile preparation of a water-based antireflective SiO2 film with high transmittance for perovskite solar cells.

The synthesis of anti-reflective (AR) films has been increasingly focused on environmental friendliness and cost efficiency in order to realize green and sustainable development. Herein, a novel strategy for preparing a nanoporous SiO2 AR film with high transmittance by a sol-gel process is proposed based on a sodium silicate aqueous solution. Sodium ions in the as-prepared SiO2 AR film can be effectively removed by a facile washing process, and thus its refractive index can be regulated. Moreover, the pH value of the sol has a huge effect on the structure and properties of the SiO2 AR film. As a result, the AR film exhibited a high transmittance increase of 4.10% at 550 nm and an average transmittance increase by 3.51% in the wavelength range of 380-1100 nm compared with blank glass. In addition, the obtained water-based SiO2 AR film exhibited hydrophilicity and the water contact angle (WCA) can be regulated from 61° to 8.4°. When the AR film was applied to the upper surface of perovskite solar cells, the photoelectric conversion efficiency (PCE) revealed an improvement of 1.44% compared with the PCE of perovskite solar cells without the AR film. Therefore, this work can provide a facile and effective method to prepare water-based antireflective films with high transmittance for solar cells.

Two-Dimensional SnS Mediates NiFe-LDH-Layered Electrocatalyst toward Boosting OER Activity for Water Splitting.

NiFe-layered double hydroxides (NiFe-LDHs), as promising electrocatalysts, have received significant research attention for hydrogen and oxygen generation through water splitting. However, the slow oxidation kinetics of NiFe-LDH, due to the limited number of active sites and the low conductivity, hinders the improvement of the water-splitting efficiency. Therefore, to overcome the obstacles, two-dimensional (2D) SnS was first explored to tailor the prepared NiFe-LDH via the hydrothermal method. A NiFe-LDH/SnS heterojunction is built, which is observed from the microstructural investigations. SnS incorporation could greatly improve the conductivity of the NiFe-LDH sheets, which was reflected by the reduced charge transfer resistance. Moreover, SnS layers modulated the electronic environment around the active sites, favoring the adsorption of intermediates during the oxygen evolution reaction (OER) process, which was verified by density functional theory calculations. A synergistic effect induced by the NiFe-LDH/SnS heterostructure promoted the OER activities in electrical, electronic, and energetic aspects. Consequently, the as-prepared NiFe-LDH/SnS electrocatalyst greatly improved the electrocatalytic performance, exhibiting 20% and 27% reductions in the overpotential and Tafel slope compared with those of pristine NiFe-LDH, respectively. The results provide a strategy for regulating NiFe-based electrocatalysts by using emerging 2D materials to enhance water-splitting efficiency.

Enhanced Thermochromic Performance of VO2 Nanoparticles by Quenching Process.

Vanadium dioxide (VO2) has been a promising energy-saving material due to its reversible metal-insulator transition (MIT) performance. However, the application of VO2 films has been seriously restricted due to the intrinsic low solar-energy modulation ability (ΔTsol) and low luminous transmittance (Tlum) of VO2. In order to solve the problems, the surface structure of VO2 particles was regulated by the quenching process and the VO2 dispersed films were fabricated by spin coating. Characterizations showed that the VO2 particles quenched in deionized water or ethanolreserved VO2(M) phase structure and they were accompanied by surface lattice distortion compared to the pristine VO2. Such distortion structure contributed to less aggregation and highly individual dispersion of the quenched particles in nanocomposite films. The corresponding film of VO2 quenched in water exhibited much higher ΔTsol with an increment of 42.5% from 8.8% of the original VO2 film, because of the significant localized surface plasmon resonance (LSPR) effect. The film fabricated from the VO2 quenched in ethanol presented enhanced thermochromic properties with 15.2% of ΔTsol and 62.5% of Tlum. It was found that the excellent Tlum resulted from the highly uniform dispersion state of the quenched VO2 nanoparticles. In summary, the study provided a facile way to fabricate well-dispersed VO2 nanocomposite films and to facilitate the industrialization development of VO2 thermochromic films in the smart window field.

Facile Synthesis of ZrO2-SiO2 Antireflective Films with Good Mechanical Performances for Perovskite Solar Cells.

Antireflective (AR) films are widely applied in solar cells to reduce the reflectivity toward sunlight, thus improving the photoelectric conversion efficiency (PCE) of solar cells. However, AR films are still suffering from poor mechanical properties and low transmittance in photovoltaic applications. Herein, a ZrO2-SiO2 composite film with enhanced mechanical properties was successfully synthesized by a facile sol-gel method, whose pencil hardness increased from less than 6B to B compared with the pure SiO2 film synthesized with the same alkali-catalyzed method. Moreover, the ZrO2-SiO2 film with a Zr/Si mole ratio (nZr/Si) of 0.06 exhibited a high transmittance gain (ΔT) of 3.0%, and an obvious increase (1.32%) in PCE was observed in a perovskite solar cell compared with the cell covered by a bare glass. Additionally, both the short-circuit current density (JSC) and PCE of perovskite solar cells have a non-linear increasing relationship with the average transmittance (Tavg) of the ZrO2-SiO2 composite film. In this sense, this work can provide a facile way to prepare AR films effectively improving performances of solar cells.

Enhanced Luminescence of Dye-Decorated ZIF-8 Composite Films via Controllable D-A Interactions for White Light Emission.

Metal-organic frameworks (MOFs) constructed by metal ions/clusters and organic linkers are used to encapsulate fluorescent guest species with aggregation-caused quenching (ACQ) effects to enhance fluorescence properties due to their porous structures and high specific surface areas. However, there would be a problem of matching between MOF pores and guest molecules' sizes. In this paper, amorphous ZIF-8 was modified by carboxyl functional groups (H3BTC-ZIF-8) via introducing the 1,2,4-benzenetricarbonic acid (H3BTC) ligand into the ZIF-8 sol system. Moreover, H3BTC-ZIF-8 was used for the loading of organic fluorescent dyes rhodamine 6G (R6G) and coumarin 151 (C151) to prepare R6G/C151/H3BTC-ZIF-8 composite films. A white-light-emitting composite film (R6G/C151/H3BTC-ZIF-8) with CIE coordinates of (0.323, 0.347) was successfully prepared by compounding fluorescent dyes (R6G and C151) with H3BTC-modified ZIF-8, whose photoluminescence quantum yield (PLQY) can reach 64.0%. It was higher than the PLQY of the composite films prepared by crystalline ZIF-8 (40.2%) or amorphous ZIF-8 without H3BTC (48.0%) compounded with the same concentrations of dyes. The fluorescence enhancement was probably attributed to an increased amount of active sites of H3BTC-modified ZIF-8 interacting with dyes C151 and R6G. This can form hydrogen bonds between H3BTC-ZIF-8 and C151, and weak electron donor-acceptor (D-A) interactions between H3BTC-ZIF-8 and R6G molecules, respectively, thus enhancing the interactions between dyes and ZIF-8 and reducing the ACQ effect existing between dye molecules. Therefore, this strategy could provide an important guidance to develop white-light-emissive materials.

A Semiconductor Biohybrid System for Photo-Synergetic Enhancement of Biological Hydrogen Production.

CdS nanoparticles were introduced on E. coli cells to construct a hydrogen generating biohybrid system via the biointerface of tannic acid-Fe complex. This hybrid system promotes good biological activity in a high salinity environment. Under light illumination, the as-synthesized biohybrid system achieves a 32.44 % enhancement of hydrogen production in seawater through a synergistic effect.

Facile Solution Process of VO2 Film with Mesh Morphology for Enhanced Thermochromic Performance.

The fabrication and applications of VO2 film continue to be of considerable interest due to their good thermochromic performance for smart windows. However, low visible transmittance (Tlum) and solar modulation efficiency (∆Tsol) impede the application of VO2 film, and they are difficult to improve simultaneously. Here, a facile zinc solution process was employed to control the surface structure of dense VO2 film and the processed VO2 film showed enhanced visible transmittance and solar modulation efficiency, which were increased by 7.5% and 9.5%, respectively, compared with unprocessed VO2 film. This process facilitated the growth of layered basic zinc acetate (LBZA) nanosheets to form mesh morphology on the surface of VO2 film, where LBZA nanosheets enhance the visible transmittance as an anti-reflection film. The mesh morphology also strengthened the solar modulation efficiency with small caves between nanosheets by multiplying the times of reflection. By increasing the zinc concentration from 0.05 mol/L to 0.20 mol/L, there were more LBZA nanosheets on the surface of the VO2 film, leading to an increase in the solar/near-infrared modulation efficiency. Therefore, this work revealed the relationship between the solution process, surface structure, and optical properties, and thus can provide a new method to prepare VO2 composite film with desirable performance for applications in smart windows.

Modulation of Structure and Optical Property of Nitrogen-Incorporated VO2 (M1) Thin Films by Polyvinyl Pyrrolidone.

VO2, as a promising material for smart windows, has attracted much attention, and researchers have been continuously striving to optimize the performance of VO2-based materials. Herein, nitrogen-incorporated VO2 (M1) thin films, using a polyvinylpyrrolidone (PVP)-assisted sol-gel method followed by heat treatment in NH3 atmosphere, were synthesized, which exhibited a good solar modulation efficiency (ΔTsol) of 4.99% and modulation efficiency of 37.6% at 2000 nm (ΔT2000 nm), while their visible integrated transmittance (Tlum) ranged from 52.19% to 56.79% after the phase transition. The crystallization, microstructure, and thickness of the film could be regulated by varying PVP concentrations. XPS results showed that, in addition to the NH3 atmosphere-N doped into VO2 lattice, the pyrrolidone-N introduced N-containing groups with N-N, N-O, or N-H bonds into the vicinity of the surface or void of the film in the form of molecular adsorption or atom (N, O, and H) filling. According to the Tauc plot, the estimated bandgap of N-incorporated VO2 thin films related to metal-to-insulator transition (Eg1) was 0.16-0.26 eV, while that associated with the visible transparency (Eg2) was 1.31-1.45 eV. The calculated Eg1 and Eg2 from the first-principles theory were 0.1-0.5 eV and 1.4-1.6 eV, respectively. The Tauc plot estimation and theoretical calculations suggested that the combined effect of N-doping and N-adsorption with the extra atom (H, N, and O) decreased the critical temperature (τc) due to the reduction in Eg1.

Facile Synthesis of Island-like ZrO2-VO2 Composite Films with Enhanced Thermochromic Performance for Smart Windows.

VO2-based film, as a very promising thermochromic material for smart windows, has attracted extensive attention but has not been widely applied because it is difficult to simultaneously improve in terms of both solar-modulation efficiency (ΔTsol) and visible transmittance (Tlum) when made using the magnetron-sputtering method, and it has poor durability when made using the wet chemical method. Herein, island-like ZrO2-VO2 composite films with improved thermochromic performance (ΔTsol: 12.6%, Tlum: 45.0%) were created using a simple approach combining a dual magnetron-sputtering and acid-solution procedure. The film's ΔTsol and Tlum values were increased initially and subsequently declined as the sputtering power of the ZrO2 target was raised from 30 W to 120 W. ΔTsol achieved its maximum of 12.6% at 60 W, and Tlum reached its maximum of 51.1% at 90 W. This is likely the result of the interaction of two opposing effects: Some VO2 nanocrystals in the composite film were isolated by a few ZrO2 grains, and some pores could utilize their surface-plasmon-resonance effect at high temperature to absorb some near-infrared light for an enhanced ΔTsol and Tlum. More ZrO2 grains means fewer VO2 grains in the composite film and increased film thickness, which also results in a decrease in ΔTsol and Tlum. As a result, this work may offer a facile strategy to prepare VO2-based films with high thermochromic performance and promote their application in smart windows.

Acid Solution Processed VO2-Based Composite Films with Enhanced Thermochromic Properties for Smart Windows.

As a typical thermochromic material, VO2 coatings can be applied to smart windows by modulating the transmission of near infrared (NIR) light via phase transition. However, the inherent undesirable luminous transmittance (Tlum) and solar modulation efficiency (ΔTsol) of pure VO2 impede its practical application. In order to solve this problem, the porous VO2 based composite film was prepared by magnetron sputtering and subsequent acid solution process with Zn2V2O7 particles used as a sacrificial template to create pores, which showed excellent Tlum (72.1%) and enhanced ΔTsol (10.7%) compared with pure VO2 film. It was demonstrated that the porous structure of the film caused by acid solution process could improve the Tlum obviously and the isolated VO2 nanoparticles presented strong localized surface plasmon resonance (LSPR) effects to enhance the ΔTsol. Therefore, this method will provide a facile way to prepare VO2 based films with excellent thermochromic performance and thus promote the application of the VO2 based films in smart windows.

Deep-red emitting zinc and aluminium co-doped copper indium sulfide quantum dots for luminescent solar concentrators.

Pure CuInS2 quantum dots (CIS QDs) exhibited poor photoluminescent (PL) performance due to more dangling bonds on their surface and thus needed a shell to form core@shell structured QDs. However, conventional shells had a higher band gap than CIS QDs so that the core@shell structured QDs showed a blue-shifted PL peak below 700 nm and narrower light absorption range. Herein, Zn and Al co-doped CIS QDs were synthesized by a facile cation exchanged method which can significantly improve the PL property emitting at ∼740 nm compared to pure CIS QDs. The enhancement of the PL property was probably attributed to ZnCu and AlCu defects in the CIS QDs which could cause electron-hole radiative recombination via defect levels, reduce the number of dangling bonds and thus minimize the nonradiative recombination through surface electron trapping. Furthermore, the PL intensity was controlled by doping time and reached the maximum at 30 min. The obtained deep-red emitting CIS QDs were employed to fabricate semi-transparent luminescent solar concentrators (LSCs) which exhibited an excellent optical efficiency of 6.97%. The success in using such Zn and Al co-doped CIS QDs could pave the way to realize high efficiency and environment-friendly LSCs for building integrated photovoltaics.

Mesoporous ZnO nanorods array with a controllable area density for enhanced photocatalytic properties.

Usually, a ZnO nanorods array exhibits a relatively small effective surface area due to its smooth surface and large area density (the number of ZnO nanorods per unit area). In this work, a mesoporous ZnO nanorods array with a small area density and a large effective surface area was successfully synthesized on the surface of fluorine-doped tin dioxide (FTO) glass using a facile solution process, with ethylene glycol (EG) and water serving as the mixed solvent and cadmium ions serving as an additives. The area density, aspect ratio and specific surface area of mesoporous ZnO nanorods array can be controlled by adjusting the concentration of cadmium ions in the EG-H2O mixed solution. The obtained ZnO nanorods array was applied as the photocatalyst for the photodegradation of methylene blue (MB) and showed a good catalytic performance that was dependent on the area density, rather than the specific surface area. This may be because a smaller area density of nanorods array can facilitate the diffusion of MB molecules and thus provide a larger effective surface area for MB adsorption, despite a large difference in their specific surface area. Therefore, this work can provide a guidance for synthesizing nanostructures with good photocatalytic activity on the devices.

High selectivity of sulfur-doped SnO2 in NO2 detection at lower operating temperatures.

Resistive gas sensors based on metal oxides have aroused great interest in the sensing of NO2 gas due to their low cost, good stability, and easy fabrication. However, drawbacks such as low sensitivity and a lack of selectivity, which originate from the limited kinds of intrinsic active centers on the surface of the metal oxides that could be involved in the gas-sensing reaction, remain great challenges to overcome. To solve these problems, surface modification of SnO2 by S-doping was carried out by the sintering of flower-like SnS2. Gas-sensing tests revealed that the S-doped SnO2 showed ultra-high sensitivity to NO2 (Rg/Ra = 600 toward 5 ppm) with low optimal operating temperature (50 °C). The detection limit of the sensor was as low as 50 ppb (Rg/Ra = 11). Notably, the S-doped SnO2 showed negligible cross-responses to alcohol, acetone, HCHO, SO2, H2S, and xylene. The ultra-high sensitivity and selectivity toward NO2 were closely related to the content of the S-dopant. This phenomenon is attributed to the active role of S-dopant during the surface reactions with NO2, which was substantiated by in situ Raman characterization and DFT-based calculations. This study offers an important guide for surface modification by doping to improve the sensitivity and selectivity of metal oxides and sheds new light on material design to develop resistive gas sensors for NO2 detection.

Nanocomplexes from RGD-modified generation 1.0 polyamidoamine based copolymers used for intravascular gene release to prevent restenosis.

AIM: To validate the efficacy of nanocomplexes from RGD-modified polyamidoamine (PAMAM G1) copolymer for prevention of restenosis. MATERIALS & METHODS: Generation 1.0 polyamidoamine (PAMAM G1)-based copolymers (PGP) and RGD modified PGP (PGP-RGD) were synthesized and its properties were evaluated. Intravascular VEGF165 release tests were performed. RESULTS: The PGP-RGD1 (2.6% grafting rate) exhibited lower cytotoxicity and larger combining ability with pDNA. The complexes had sizes of 80-160 nm and zeta potentials of 3-20 mV. Transfection efficiency of PGP-RGD1 complexes in human umbilical vein endothelial cells was larger than that of PGP complexes. Patency and expression level of artery in PGP-RGD1 group were higher than that in saline group. CONCLUSION: PGP-RGD1 will be a promising targeted gene vector.

Surface doping of La ions into ZnO nanocrystals to lower the optimal working temperature for HCHO sensing properties.

Lowering the working temperature without sacrificing other good gas-sensing properties is of particular interest to gas sensors for an excellent performance. In this work, La surface doped ZnO nanocrystals were successfully prepared by a facile thermal treatment with lanthanum nitrate (La(NO3)3) solution injected into ZnO thick films, which exhibited a remarkable decrease in the optimal working temperature for formaldehyde (HCHO) sensing properties. This was probably attributed to the formation of surface LaZn defects in the ZnO nanocrystals which was evidenced by XRD, XPS results and DFT calculations. The surface LaZn defects can introduce a shallower donor level than oxygen vacancies, and probably facilitate the charge transfer from oxygen species to ZnO for producing chemisorbed oxygen species more easily. This was in good agreement with the DFT results that the absorption energy of oxygen molecules on the surface of La doped ZnO was only -10.61 eV, much lower than that of pure ZnO. Moreover, the optimal working temperature of the La doped ZnO based sensor was significantly decreased from 350 to 250 °C without sacrificing the high and quick response to HCHO gas as the content of surface LaZn defects was increased gradually. Therefore, the behavior of the surface LaZn defects in the optimal working temperature revealed a HCHO response mechanism in ZnO, which can provide new insights into the enhanced HCHO sensing performance of gas sensors.

Endothelial cell-targeted pVEGF165 polyplex plays a pivotal role in inhibiting intimal thickening after vascular injury.

Upregulation of vascular endothelial growth factor (VEGF) expression can inhibit intimal thickening after vascular injury. However, the lack of efficient gene delivery systems leads to insufficient VEGF expression, which prevents its application in gene therapy. In the present study, to improve the delivery of the plasmid vector with the VEGF gene (pVEGF165) to the injured vessel wall, we explored the potentially important difference between endothelial cell-targeted and nontargeted polymeric carriers. The αvß3 integrin is overexpressed on activated endothelial cells but not on normal quiescent vessels. In this study, CDG2-cRGD, synthesized by conjugating an αvß3 integrin-binding cyclic arginylglycylaspartic acid (cRGD) peptide with the Generation 2 polycation polyamidoamine (PAMAMG2)-g-cyclodextrin (termed as CDG2), was developed as a targetable carrier. It was observed that the specific integrin-ligand interactions greatly enhanced cellular internalization of CDG2-cRGD in human umbilical vein endothelial cells (HUVECs), which are notoriously difficult to transfect. Consequently, HUVECs were found to show remarkably high levels of VEGF165 expression induced by the CDG2-cRGD polyplex. Interestingly, VEGF165 overexpression in vivo was more complex than that in vitro, and in vivo assays demonstrated that the stimulus response to balloon injury in arteries could obviously upregulate VEGF165 expression in the saline-treated group, although it was not enough to prevent intimal thickening. In gene-transfected groups, intravascular delivery of pVEGF165 with the CDG2-cRGD polyplex into rabbits after vascular injury resulted in a significant inhibition of intimal thickening at 4 weeks, whereas the low therapeutic efficacy in the nontargeted CDG2-treated group was only comparable to that in the saline-treated group. It is becoming clear that the conflicting results of VEGF165 gene therapy in two gene-transfected groups are reflective of the pivotal role of the cRGD-conjugated carriers in achieving the beneficial therapeutic effects of vascular gene therapy.

Interface Bonds Determined Gas-Sensing of SnO2-SnS2 Hybrids to Ammonia at Room Temperature.

Unique gas-sensing properties of semiconducting hybrids that are mainly related to the heterogeneous interfaces have been considerably reported. However, the effect of heterogeneous interfaces on the gas-sensing properties is still unclear, which hinders the development of semiconducting hybrids in gas-sensing applications. In this work, SnO2-SnS2 hybrids were synthesized by the oxidation of SnS2 at 300 °C with different times and exhibited high response to NH3 at room temperature. With the increasing oxidation time, the relative concentration of interfacial Sn bonds, O-Sn-S, among the total Sn species of the SnO2-SnS2 hybrids increased first and then decreased. Interestingly, it can be found that the response of SnO2-SnS2 hybrids to NH3 at room temperature exhibited a strong dependence on the interfacial bonds. With more chemical bonds at the interface, the lower interface state density and the higher charge density of SnO2 led to more chemisorbed oxygen, resulting in a high response to NH3. Our results revealed the real roles of the heterogeneous interface in gas-sensing properties of hybrids and the importance of the interfacial bonds, which offers guidance for the material design to develop hybrid-based sensors.

Divalent folate modification on PEG: an effective strategy for improving the cellular uptake and targetability of PEGylated polyamidoamine-polyethylenimine copolymer.

The stability and targeting ability of nanocarrier gene delivery systems are necessary conditions to ensure the good therapeutic effect and low nonspecific toxicity of cancer treatment. Poly(ethylene glycol) (PEG) has been widely applied for improving stability and as a spacer for linking ligands and nanocarriers to improve targetability. However, the cellular uptake and endosomal escape capacity of nanocarriers has been seriously harmed due to the introduction of PEG. In the present study, we synthesized a new gene delivery vector by coupling divalent folate-PEG (PEG3.4k-FA2) onto polyamidoamine-polyethylenimine (PME) copolymer (PME-(PEG3.4k-FA2)1.72). Both PEG and monovalent folate-PEG (PEG3.4k-FA1) modified PME were prepared as control polymers, which were named as PME-(PEG3.5k)1.69 and PME-(PEG3.4k-FA1)1.66, respectively. PME-(PEG3.4k-FA2)1.72 exhibited strong DNA condensation capacity like parent polymer PME which was not significantly influenced by PEG. PME-(PEG3.4k-FA2)1.72/DNA complexes at N/P = 10 had a diameter ∼143 nm and zeta potential ∼13 mV and showed the lowest cytotoxicity and hemolysis and the highest transfection efficiency among all tested polymers. In folate receptor positive (FR-positive) cells, the cellular uptake and transfection efficiency were increased with the increase in the number of folates coupled on PEG; the order was PME-(PEG3.4k-FA2)1.72 > PME-(PEG3.4k-FA1)1.66 > PME-(PEG3.5k)1.69. Folate competition assays showed that PME-(PEG3.4k-FA2)1.72 complexes had stronger targeting ability than PME-(PEG3.5k)1.69 and PME-(PEG3.4k-FA1)1.66 complexes due to their higher folate density per PEG molecule. Cellular uptake mechanism study showed that the folate density on PEG could change the endocytosis pathway of PME-(PEG3.5k)1.69 from clathrin-mediated endocytosis to caveolae-mediated endocytosis, leading to less lysosomal degradation. Distribution and uptake in 3D multicellular spheroid assays showed that divalent folate could offer PME-(PEG3.4k-FA2)1.72 complexes stronger penetrating ability and higher cellular uptake. With these advantages, PME-(PEG3.4k-FA2)1.72 may be a promising nonviral vector candidate for efficient gene delivery. This study also indicates that divalent folate modification on PEG can serve as an efficient strategy to improve the cellular uptake and targeting ability of PEGylated cationic polymers for gene delivery.

Dilution-stable PAMAM G1-grafted polyrotaxane supermolecules deliver gene into cells through a caveolae-dependent pathway.

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.