Chemical and Physical Architecture of Macromolecular Gels for Fracturing Fluid Applications in the Oil and Gas Industry; Current Status, Challenges, and Prospects.

Hydraulic fracturing is vital in recovering hydrocarbons from oil and gas reservoirs. It involves injecting a fluid under high pressure into reservoir rock. A significant part of fracturing fluids is the addition of polymers that become gels or gel-like under reservoir conditions. Polymers are employed as viscosifiers and friction reducers to provide proppants in fracturing fluids as a transport medium. There are numerous systems for fracturing fluids based on macromolecules. The employment of natural and man-made linear polymers, and also, to a lesser extent, synthetic hyperbranched polymers, as additives in fracturing fluids in the past one to two decades has shown great promise in enhancing the stability of fracturing fluids under various challenging reservoir conditions. Modern innovations demonstrate the importance of developing chemical structures and properties to improve performance. Key challenges include maintaining viscosity under reservoir conditions and achieving suitable shear-thinning behavior. The physical architecture of macromolecules and novel crosslinking processes are essential in addressing these issues. The effect of macromolecule interactions on reservoir conditions is very critical in regard to efficient fluid qualities and successful fracturing operations. In future, there is the potential for ongoing studies to produce specialized macromolecular solutions for increased efficiency and sustainability in oil and gas applications.

Recent Developments on Electroactive Organic Electrolytes for Non-Aqueous Redox Flow Batteries: Current Status, Challenges, and Prospects.

The ever-increasing threat of climate change and the depletion of fossil fuel resources necessitate the use of solar- and wind-based renewable energy sources. Large-scale energy storage technologies, such as redox flow batteries (RFBs), offer a continuous supply of energy. Depending on the nature of the electrolytes used, RFBs are broadly categorized into aqueous redox flow batteries (ARFBs) and non-aqueous redox flow batteries (NARFBs). ARFBs suffer from various problems, including low conductivity of electrolytes, inferior charge/discharge current densities, high-capacity fading, and lower energy densities. NARFBs offer a wider potential window and range of operating temperatures, faster electron transfer kinetics, and higher energy densities. In this review article, a critical analysis is provided on the design of organic electroactive molecules, their physiochemical/electrochemical properties, and various organic solvents used in NARFBs. Furthermore, various redox-active organic materials, such as metal-based coordination complexes, quinones, radicals, polymers, and miscellaneous electroactive species, explored for NARFBs during 2012-2023 are discussed. Finally, the current challenges and prospects of NARFBs are summarized.

Development of Membranes and Separators to Inhibit Cross-Shuttling of Sulfur in Polysulfide-Based Redox Flow Batteries: A Review.

The global rapid transition from fossil fuels to renewable energy resources necessitates the implementation of long-duration energy storage technologies owing to the intermittent nature of renewable energy sources. Therefore, the deployment of grid-scale energy storage systems is inevitable. Sulfur-based batteries can be exploited as excellent energy storage devices owing to their intrinsic safety, low cost of raw materials, low risk of environmental hazards, and highest theoretical capacities (gravimetric: 2600 Wh/kg and volumetric: 2800 Wh/L). However, sulfur-based batteries exhibit certain scientific limitations, such as polysulfide crossover, which causes rapid capacity decay and low Coulombic efficiency, thereby hindering their implementation at a commercial scale. In this review article, we focus on the latest research developments between 2012-2023 to improve the separators/membranes and overcome the shuttle effect associated with them. Various categories of ion exchange membranes (IEMs) used in redox batteries, particularly polysulfide redox flow batteries and lithium-sulfur batteries, are discussed in detail. Furthermore, advances in IEM constituents are summarized to gain insights into different fundamental strategies for attaining targeted characteristics, and a critical analysis is proposed to highlight their efficiency in mitigating sulfur cross-shuttling issues. Finally, future prospects and recommendations are suggested for future research toward the fabrication of more effective membranes with desired properties.

Recent Development of Electrolytes for Aqueous Organic Redox Flow Batteries (Aorfbs): Current Status, Challenges, and Prospects.

In recent years, aqueous organic redox flow batteries (AORFBs) have attracted considerable attention due to advancements in grid-level energy storage capacity research. These batteries offer remarkable benefits, including outstanding capacity retention, excellent cell performance, high energy density, and cost-effectiveness. The organic electrolytes in AORFBs exhibit adjustable redox potentials and tunable solubilities in water. Previously, various types of organic electrolytes, such as quinones, organometallic complexes, viologens, redox-active polymers, and organic salts, were extensively investigated for their electrochemical performance and stability. This study presents an overview of recently published novel organic electrolytes for AORFBs in acidic, alkaline, and neutral environments. Furthermore, it delves into the current status, challenges, and prospects of AORFBs, highlighting different strategies to overcome these challenges, with special emphasis placed on their design, composition, functionalities, and cost. A brief techno-economic analysis of various aqueous RFBs is also outlined, considering their potential scalability and integration with renewable energy systems.

Optical Chemical Sensing of Iodide Ions: A Comprehensive Review for the Synthetic Strategies of Iodide Sensing Probes, Challenges, and Future Aspects.

Among several anions, iodide (I- ) ions play a crucial role in human biological activities. In it's molecular form (I2 ), iodine is utilized for several industrial applications such as syntheses of medicines, fabric dyes, food additives, solar cell electrolytes, catalysts, and agrochemicals. The excess or deficiency of I- ions in the human body and environmental samples have certain consequences. Therefore, the selective and sensitive detection of I- ions in the human body and environment is vital for monitoring their overall profile. Amongst various analytical techniques for the estimation of I- ions, optical-chemical sensing possesses the merits of high sensitivity, selectivity, and utilizing the least amount of sensing materials. The distinctive aims of this manuscript are (i) To comprehensively review the development of optical chemical sensors (fluorescent & colorimetric) reported between 2001-2021 using organic fluorescent molecules, supramolecular materials, conjugated polymers, and metal-organic frameworks (MOFs). (ii) To illustrate the design and synthetic strategies to create specific binding and high affinity of I- ions which could help minimize negative consequences associated with its large size and high polarizability. (iii) The challenges associated with sensitivity and selectivity of I- ions in aqueous and real samples. The probable future aspects concerning the optical chemical detection of I- ions have also been discussed in detail.

Enhanced Antimicrobial Activity of Biofunctionalized Zirconia Nanoparticles.

The effective interactions of nanomaterials with biological constituents play a significant role in enhancing their biomedicinal properties. These interactions can be efficiently enhanced by altering the surface properties of nanomaterials. In this study, we demonstrate the method of altering the surface properties of ZrO2 nanoparticles (NPs) to enhance their antimicrobial properties. To do this, the surfaces of the ZrO2 NPs prepared using a solvothermal method is functionalized with glutamic acid, which is an α-amino acid containing both COO- and NH4 + ions. The binding of glutamic acid (GA) on the surface of ZrO2 was confirmed by UV-visible and Fourier transform infrared spectroscopies, whereas the phase and morphology of resulting GA-functionalized ZrO2 (GA-ZrO2) was identified by X-ray diffraction and transmission electron microscopy. GA stabilization has altered the surface charges of the ZrO2, which enhanced the dispersion qualities of NPs in aqueous media. The as-prepared GA-ZrO2 NPs were evaluated for their antibacterial properties toward four strains of oral bacteria, namely, Rothia mucilaginosa, Rothia dentocariosa, Streptococcus mitis, and Streptococcus mutans. GA-ZrO2 exhibited increased antimicrobial activities compared with pristine ZrO2. This improved activity can be attributed to the alteration of surface charges of ZrO2 with GA. Consequently, the dispersion properties of GA-ZrO2 in the aqueous solution have increased considerably, which may have enhanced the interactions between the nanomaterial and bacteria.

Sensitization of Cancer Cells via Non-Viral Delivery of Apoptosis Inducing Proteins Using a Cationic Bolaamphiphile.

Cationic bolaamphiphile polymers had been previously studied as efficient delivery system for the delivery of proteins with relatively low toxicity. Here, the authors investigate the use of a protein delivery system based on a cationic bolaamphiphile to sensitize cancer cells toward apoptosis-inducing drugs as a novel approach for cancer therapy. The authors demonstrates the efficacy of the system by two strategies. The first strategy involves delivery of a survivin antibody to inhibit survivin activity. Sensitization of MCF-7 cells to doxorubicin is observed by survivin inhibition by antibodies. The IC50 of doxorubicin is reduced ≈2.5-fold after delivery of survivin antibodies to breast cancer cells and induction of apoptosis is shown by Western blotting with apoptosis specific antibodies. In a second approach, functional wild type p53 is delivered into p53-null liver cancer (Hep3B) cells, sensitizing the cells toward the p53 pathway drug, Nutlin. Nutlin reduced the viability of Hep3B cells by ≈42% at 15 µM concentration, demonstrating the effectiveness of p53 delivery. The expression of p21, a downstream target of p53 further confirmed the functional status of the delivered protein. In conclusion. The successful delivery of apoptosis inducing proteins and sensitization of cancer cells via cationic bolaamphiphile polymer represents a promising system for cancer therapeutics.

Supramolecular nanoparticle carriers self-assembled from cyclodextrin- and adamantane-functionalized polyacrylates for tumor-targeted drug delivery.

The advancement of nanobiotechnology has led to the development of various techniques for addressing target-specific drug delivery issues. In this article, we successfully developed a supramolecular self-assembly approach for the fabrication of polyacrylate-based nanoparticles with simultaneous loading of the anticancer drug doxorubicin (DOX) for targeted delivery towards cancer treatment in vitro and in vivo. Two types of polyacrylates functionalized with adamantane and ß-cyclodextrin respectively could self-assemble to form supramolecular nanoparticles through strong host-guest complexation between adamantane and ß-cyclodextrin. Folic acid was incorporated within the supramolecular nanoparticles in order to impart the targeting specificity towards selected cancerous cell lines, namely MDA-MB231 and B16-F10. The as-synthesized supramolecular nanoparticles were fully characterized by several techniques, revealing an average nanoparticle size of 35 nm in diameter, which is small enough for excellent blood circulation. The cytotoxicity studies indicate that the supramolecular nanoparticles without drug loading were non-cytotoxic under the concentrations measured, while DOX-loaded supramolecular nanoparticles showed significant cytotoxicity. In order to investigate the targeting specificity of DOX-loaded supramolecular nanoparticles towards the cancerous cells, a healthy cell line model HEK293 was employed for carrying out the comparison studies. Due to the presence of the targeting ligand, experimental results demonstrate that the supramolecular nanoparticles were highly specific for targeting the cancerous cells, but not for HEK293 cells. After the in vitro investigations, the in vivo drug delivery study using DOX-loaded supramolecular nanoparticles was performed. Tumor-bearing nude mice were treated with DOX-loaded supramolecular nanoparticles, and the analysis results indicate that DOX-loaded supramolecular nanoparticles have the capability to enhance the therapeutic effects of DOX for effectively inhibiting the tumor growth. Thus, the self-assembled polymeric nanoparticles exhibit a highly promising potential to serve as drug carriers for targeted drug delivery towards improved cancer treatment.

Delivery of reprogramming factors into fibroblasts for generation of non-genetic induced pluripotent stem cells using a cationic bolaamphiphile as a non-viral vector.

Protein delivery allows a clinical effect to be directly realized without genetic modification of the host cells. We have developed a cationic bolaamphiphile as a non-viral vector for protein delivery application. The relatively low toxicity and efficient protein delivery by the cationic bolaamphiphile prompted us to test the system for the generation of induced pluripotent stem cells (iPSCs) as an alternative to the conventional vector-based genetic approach. Studies on the kinetics and cytotoxicity of the protein delivery system led us to use an optimized cationic bolaamphiphile-protein complex ratio of 7:1 (wt/wt) and a 3 h period of incubation with human fibroblasts, to ensure complete and non-toxic protein delivery of the reprogramming proteins. The reprogrammed cells were shown to exhibit the characteristics of embryonic stem cells, including expression of pluripotent markers, teratoma formation in SCID mice, and ability to be differentiated into a specific lineage, as exemplified by neuronal differentiation.

Rationally designed α-helical broad-spectrum antimicrobial peptides with idealized facial amphiphilicity.

A series of 12-amino acid peptide analogs is designed using point mutation strategy based on an α-helical peptide template. The first mutation in the series, KL12, has an idealized facial amphiphilicity. Subsequent mutations are performed to increase hydrophobic or cationic contents. Idealized facial amphiphilicity show enhanced antimicrobial activity and selectivity against most of the tested microbes. Increasing hydrophobic contents further enhance antimicrobial potency; however, selectivity of the most hydrophobic analog is impaired due to non-specific interactions with mammalian cell membrane. This study demonstrates that facial amphiphilicity and hydrophobic content are strongly correlated with antimicrobial activity and selectivity of antimicrobial peptides.

Advanced materials for co-delivery of drugs and genes in cancer therapy.

With cancer being the major cause of mortality worldwide, the continued development of safe and efficacious treatments is warranted. A better understanding of the molecular mechanism and genetic basis of tumor initiation and progression, coupled with advances in chemistry, molecular biology and engineering have led to discovery of a wide range of therapeutic agents for cancer therapy. However, multidrug-resistance, which is mainly caused by malfunction of genes, has become a major problem in chemotherapy. To overcome this problem, the simultaneous delivery of genes to cancer cells has been proposed to correct the malfunctioned genes to sensitize the cells to chemotherapeutics. This progress report summarizes key advances in drug and gene delivery with focus on the development of polymers, peptides, liposomes and inorganic materials as nanocarriers for co-delivery of small molecular drugs and macromolecular genes or proteins. In addition, challenges and future perspectives in the design of nanocarriers for the co-delivery of therapeutic drugs and genes are discussed.

Oligomerized alpha-helical KALA peptides with pendant arms bearing cell-adhesion, DNA-binding and endosome-buffering domains as efficient gene transfection vectors.

In this study, a number of KALA-based α-helical peptides were designed and synthesized as non-viral gene carriers. The effects of lysine and histidine residues in the pendant arms and cell-binding RGD motif on DNA binding, particle size, zeta potential, cytotoxicity and gene expression efficiency were first explored. Increasing the lysine and histidine residues reduced particle size and increased zeta potential of DNA complexes, leading to greater gene expression efficiency. In addition, the introduction of RGD group further improved gene expression level. The peptide with optimal compositions, RGDN(3)K(6)H(3)CKHLAKALAKALAC (RC29), was then oligomerized to form di-, tri- and tetra-RC29 via disulfide linkage. Upon oligomerization, RC29 attained a 3-dimensional long α-helical structure with pendant arm(s) extending transversally outwards. Each arm contains a cell-adhesion motif (RGD), DNA-binding and endosome-buffering domains(.) The α-helicity of the oligomerized peptides was evaluated by circular dichroism (CD) spectroscopy, which showed that an increased oligomerization degree led to a stronger α-helical structure. These peptides form complexes with DNA efficiently. The minimum size and maximum zeta potential of tri-RC29/DNA complexes was about 200 nm and 32.5 mV, respectively. In comparison, RC29 formed DNA complexes with a similar zeta potential, but particle size was significantly larger (355 nm). DNA complexes formed at pH 7.0 yielded higher gene expressions than those formed at pH 5.5 and 6.5. Among all the oligomerized peptides, tri-RC29 provided the highest gene expression efficiency, and its peak luciferase level was 1.5 times higher than that yielded by PEI at its optimal N/P ratio (i.e. 10). Moreover, oligomerized RC29/DNA complexes were less cytotoxic than PEI/DNA complexes. These α-helical peptides can be promising carrier for delivery of therapeutic genes in the treatment of genetic disorders.

Nanostructured PEG-based hydrogels with tunable physical properties for gene delivery to human mesenchymal stem cells.

Effective delivery of DNA to direct cell behavior in a well defined three dimensional scaffold offers a superior approach in tissue engineering. In this study, we synthesized biodegradable nanostructured hydrogels with tunable physical properties for cell and gene delivery. The hydrogels were formed via Michael addition chemistry by reacting a four-arm acrylate-terminated PEG with a four-arm thiol-functionalized PEG. Nanosized micelles self-assembled from the amphiphilic PEG-b-polycarbonate diblock copolymer, having reactive end-groups, were chemically incorporated into the hydrogel networks at various contents. The use of Michael addition chemistry allows for in situ hydrogel formation under the physiological conditions. Mechanical property analysis of the hydrogels revealed a correlation between the content of micelles and the storage modulus of the hydrogels. Internal morphology of hydrogels was observed using a field emission scanning electron microscope, which showed that the number and/or size of the pores in the hydrogel increased with increasing micelle content due to reduced crosslinking degree. There exists an optimal micelle content for cell proliferation and gene transfection. MTT assays demonstrated the highest cell viability in the hydrogel with 20% micelles. The gene expression level in hMSCs in the hydrogel with 20% micelles was also significantly higher than that in the hydrogel without micelles. The enhanced cell viability and gene expression in the hydrogel with the optimized micelle content are likely attributed to the physical properties that provide a better environment for cell-matrix interactions. Therefore, incorporating micelles into the hydrogel is a good strategy to control cellular behavior in 3-D through changes in physical properties of the microenvironment.

Diaminododecane-based cationic bolaamphiphile as a non-viral gene delivery carrier.

The advancement in gene therapy relies upon the discovery of safe and efficient delivery agents and methods. In this study, we report the design and synthesis of a cationic bolaamphiphile as a non-viral gene delivery agent. The bolaamphiphile is composed of 1,12-diaminododecane as the central hydrophobic unit linked to the hydrophilic pentaethylenehexamine via thioether-based glycidyl units. This bolaamphiphile condensed DNA efficiently into nanoparticles of sizes around 150-200 nm with positive zeta potential of 30-35 mV. In vitro luciferase expression levels and percentage of GFP expressing cells induced by the bolaamphiphile/DNA complexes were higher than those mediated by the often used "golden" standard of non-viral systems, polyethyleneimine (PEI, branched, 25 kDa) at its optimal N/P ratio in HEK293, HepG2, NIH3T3, HeLa and 4T1 cells. In vitro cytotoxicity testing revealed that the DNA complexes fabricated from this cationic bolaamphiphile displayed marginal toxicity towards all the cell lines tested. In addition, in vivo transfection studies carried out in a 4T1 mouse breast cancer model showed that the cationic bolaamphiphile delivered DNA more efficiently than PEI. This cationic bolaamphiphile may make a promising gene delivery vector for future gene therapy.

The effect of thiol functional group incorporation into cationic helical peptides on antimicrobial activities and spectra.

Antimicrobial peptides (AMP) have been proposed as blueprints for the development of new antimicrobial agents for the treatment of drug resistant infections. A series of synthetic AMPs capable of forming α-helical structures and containing free-sulfhydryl groups are designed in this study ((LLKK)(2)C, C(LLKK)(2)C, (LLKK)(3)C, C(LLKK)(3)C). In particular, the AMP with 2 cysteine residues at the terminal ends of the peptide and 2 repeat units of LLKK, i.e., C(LLKK)(2)C, has been demonstrated to have high selectivity towards a wide range of microbes from Gram-positive Bacillus subtilis, Gram-negative Escherichia coli, Pseudomonas aerogenosa, and yeast Candida albicans over red blood cells. At the MIC levels, this peptide does not induce significant hemolysis, and its MIC values occur at the concentration of more than 10 times of their corresponding 50% hemolysis concentrations (HC(50)). Microscopy studies suggest that this peptide kills microbial cells by inducing pores of ∼20-30 nm in size in microbial membrane on a short time scale, which further develops to grossly damaged membrane envelope on a longer time scale. Multiple treatments of microbes with this peptide at sub MIC concentration do not induce resistance, even up to passage 10. However, the same treatment with conventional antibiotics penicillin G or ciprofloxacin easily develop resistance in the treated microbes. In addition, the peptides are shown not to induce secretion of IFN-γ and TNF-α in human monocytes as compared to lipopolysaccharide, which implies additional safety aspects of the peptides to be used as both systemic and topical antimicrobial agents. Therefore, this study provides an excellent basis to develop promising antimicrobial agents that possess a broad range of antimicrobial activities with less susceptibility for development of drug resistance.

Pt nanoparticle label-mediated deposition of Pt catalyst for ultrasensitive electrochemical immunosensors.

Herein we describe a novel signal amplification strategy for the development of ultrasensitive electrochemical immunosensors. The amplification strategy is based on platinum catalyzing a hydrogen evolution reaction. To demonstrate its practicality, the electrochemical signal enhancement strategy has been applied for the development of a novel prostate-specific antigen (PSA) immunosensor. The immunosensing protocol utilized a gold electrode with PSA capture antibodies bound to its surface via covalent bonding. After PSA was bound to the electrode surface, a secondary platinum nanoparticle-labeled detection antibody was used to complete the sandwich immunosensor. The resulting electrode was then dipped in a platinum developer solution containing 1 mM of PtCl4(2-), 0.1M of formate (reductant) and 0.5% Tween 80 (pH 6.5) to generate bare platinum catalysts in close proximity to the Au electrode surface through a seed-mediated nucleation and growth mechanism. The signal readout was obtained electrochemically via a Pt-catalyzed hydrogen evolution reaction in an acidic aqueous medium containing 10 mM of HCl and 1 M of KCl. A detection limit of 1 fg/ml was achieved.

Branched disulfide-based polyamidoamines capable of mediating high gene transfection.

DNA condensation, endosomal escape of DNA/polymeric complexes, and unpacking of DNA are the key steps in the process of non-viral gene delivery. Amongst these steps, currently the unpacking of the DNA cargo from the DNA/polymeric nanocomplexes is the most challenging and arguably the most crucial if one wants to achieve high gene transfection with minimum cytotoxicity in the target cell. In this report we review current and past examples in the literature that demonstrate concerted efforts in designing and synthesizing various forms of cationic polymeric vectors having "built in" features. Such features can be certain types of chemical functional groups, such as amines and acids or other degradable bonds like esters, carbonates and disulfides, which allow for breakdown of polymeric vectors in certain cellular compartments. This may lead the DNA cargo to dissociate from the DNA/polymer complexes so as to maximize intracellular gene delivery. Furthermore, we provide further evidence that it is possible to achieve the goal of high gene transfection coupled with low cytotoxicity via rational design and formulation of branched polyamidoamines containing disulfide bonds. The DNA binding ability of these polymers and particle size as well as zeta potential of their DNA complexes were investigated. The cytotoxicity of pure polymer and polymer/DNA complexes at various polymer concentrations was studied in HEK293 human embryonic kidney, HepG2 human liver carcinoma, 4T1 mouse breast cancer and HeLa human cervical cancer cell lines. In vitro gene transfection efficiency induced by polymer/DNA complexes was explored in these cell lines by using luciferase and GFP reporter genes in comparison with PEI.

Brush-Like Amphoteric Poly[isobutylene-alt-(maleic acid)-graft-oligoethyleneamine)]/DNA Complexes for Efficient Gene Transfection.

Synthetic gene delivery vectors, especially cationic polymers have attracted enormous attention in recent decades because of their ease of manufacture, targettability, and scaling up. However, certain issues such as high cytotoxicity and low transfection efficiency problems have hampered the advance of nonviral gene delivery. In this study, we designed and synthesized brush-like amphoteric poly[isobutylene-alt-(maleic acid)-graft-oligoethyleneamine] capable of mediating highly efficient gene transfection. The polymers are composed of multiple pendant oligoethyleneimine molecules with alternating carboxylic acid moiety grafted onto poly[isobutylene-alt-(maleic anhydride)]. The polymer formed from pentaethylenehexamine {i.e., poly[isobutylene-alt-(maleic acid)-graft-pentaethylenehexamine)]} was able to condense DNA efficiently into nanoparticles of size around 200 nm with positive zeta potential of about 28-30 mV despite its amphoteric nature. Luciferase expression level and percentage of GFP expressing cells induced by this polymer was higher than those mediated with polyethyleneimine (branched, $\overline M _{\rm w} $ 25 kDa) by at least one order of magnitude at their optimal N/P ratios on HEK293, HepG2, and 4T1 cells. In vitro cytotoxicity testing revealed that the polymer/DNA complexes were less cytotoxic than those of PEI, and the viability of the cells after being incubated with the polymer/DNA complexes at the optimal N/P ratios was higher than 85%. This polymer can be a promising gene delivery carrier for gene therapy.

The solid-state Ag/AgCl process as a highly sensitive detection mechanism for an electrochemical immunosensor.

The highly characteristic solid-state Ag/AgCl process was used as an ultrasensitive detection mechanism for electrochemical sensors, such as a prostate-specific antigen immunosensor.

Cationic micelles self-assembled from cholesterol-conjugated oligopeptides as an efficient gene delivery vector.

Cholesterol-conjugated H(5)R(10) and H(10)R(10) oligopeptides (HR15-Chol and HR20-Chol) were designed and synthesized. These amphiphilic oligopeptides were able to self-assemble into cationic micelles in aqueous solution at low concentrations, and their critical micelle concentrations in sodium acetate buffer (20mM, pH 5.0) were 17.8 and 28.2mg/L respectively. The micelle formation was further evidenced via SEM and dynamic light scattering analyses. The average hydrodynamic size of HR15-Chol and HR20-Chol micelles was about 425 and 435 nM in diameter with zeta potential of 64 and 66 mV respectively. The formation of micelles increased local concentration of cationic charge, leading to higher DNA binding efficiency as compared to the control peptides HR15 and HR20. The minimum size observed for HR15-Chol/DNA and HR20-Chol/DNA complexes was about 175-176 nM, and the maximum zeta potential was around 61-62 mV. In comparison, HR15 and HR20 formed DNA complexes with a similar size but significantly lower zeta potential (i.e. about 31-40 mV). In particular, after being challenged by DMEM medium, the size of peptide/DNA complexes was increased significantly and their surface charge was neutralized. Nevertheless, the size of the micelle/DNA complexes formed from HR15-Chol and HR20-Chol was still about 200 nM with positive charge of around 20 mV at high N/P ratios. The micelles induced much higher overall gene expression (i.e. luciferase expression) levels than the peptides in both HepG2 and HEK293 cell lines. Increasing the histidine residue from 0 to 5 to 10 further increased gene expression efficiency. In particular, HR20-Chol micelles yielded 95% GFP-positive HepG2 cells at N/P 50, much higher than that induced by PEI at its optimal N/P ratio (i.e. 10), which was 6.8%. In 4T1 cells, HR20-Chol induced 2 times higher luciferase expression level than PEI at their optimal N/P ratios. Moreover, HR20-Chol micelle/DNA complexes were less cytotoxic than PEI/DNA complexes. These micelles may be a promising carrier for delivery of therapeutic genes.