Multiple Swellings Over the Scrotum: Epidermal Inclusion Cysts.

Epidermal inclusion cysts are lesions that are benign and commonly occur on the regions of the scalp, face, neck, and scrotum. It is usually a painless condition but may become painful if it gets infected. A rupture of the cyst wall can lead to an intensely painful inflammatory reaction, and it is a common presentation to a surgeon. In this case, the patient reported multiple painless swellings on the scrotum, which were excised under spinal anesthesia. It was initially thought to be trichilemmal cysts, but on histopathological examination (HPE), it was diagnosed as epidermal inclusion cysts.

The Constitutional Isomerism of One-Component Ionizable Amphiphilic Janus Dendrimers Orchestrates the Total and Targeted Activities of mRNA Delivery.

Constitutional isomerism has been previously demonstrated by one of our laboratories to represent a powerful design strategy for the elaboration of complex functional self-organizations. Here we report the design, synthesis, and characterization of 14 positional, skeletal, and functional constitutional isomeric one-component, multifunctional, sequence-defined, amphiphilic ionizable Janus dendrimers (IAJDs). Their coassembly by simple injection with luciferase mRNA (Luc-mRNA) to form dendrimersome nanoparticles (DNPs) was studied. Subsequently, the resulting DNPs were employed to investigate, with screening experiments, the delivery of Luc-mRNA in vivo. Constitutional isomerism was shown to produce changes of up to two orders of magnitude of the total-body luciferase activity and targeted luciferase activity to the spleen and liver, of up to three orders of magnitude difference in targeted luciferase activity to the lungs and up to six orders of magnitude to lymph nodes. These results indicate that constitutional isomerism may represent not only a simple but also an important synthetic strategy that most probably may impact the activity of all components of synthetic vectors used in RNA-based nanomedicine, including in mRNA vaccines and therapeutics.

Effect of Niosomal Encapsulation of Quercetin and Silymarin and their Combination on Dimethylnitrosoamine-induced and Phenobarbitalpromoted Hepatocellular Carcinoma in Rat Model.

BACKGROUND: Hepatocellular carcinoma is a particularly dangerous and severe kind of liver cancer. Many anticancer drugs fail to complete the treatment of hepatocellular carcinoma without any side effects. There should be appropriate and without side effective treatments for hepatocellular carcinoma. OBJECTIVE: The objective of the current study was to evaluate how quercetin and silymarin in a niosomal formulation affected hepatocyte carcinoma caused by diethylnitrosamine. METHODS: Five groups were created from the thirty male rats. Normal control (untreated group), tumor group (administered dimethylnitrosoamine 200mg/kg), treatment group I (administered 50 mg/kg of niosomal encapsulated quercetin), treatment group II (administered 50 mg/kg of niosomal encapsulated silymarin), and treatment group III (administered 50 mg/kg of niosomal encapsulated quercetin + silymarin). Then, biochemical estimation, serum analysis, and histopathological examination were carried out. RESULTS: Treatment group III, treated with niosomal encapsulation of a combination of quercetin + silymarin 50 mg/kg, demonstrated the significant restoration of alpha-fetoprotein and carcinoembryonic antigen and also antioxidants like superoxide dismutase and nitric oxide. The histopathological examination showed improved liver architecture in this group compared to other treatment groups. CONCLUSION: Our findings revealed that a potent anticancer effect was observed in treatment group III as niosomal formulation increased the bioavailability of the drug within the body. In order to completely understand the underlying processes and evaluate the therapeutic effectiveness of these chemicals in the therapy of hepatocellular carcinoma, further investigation and clinical trials are required.

Targeted and Equally Distributed Delivery of mRNA to Organs with Pentaerythritol-Based One-Component Ionizable Amphiphilic Janus Dendrimers.

Delivery of nucleic acids with viral and synthetic vectors has pioneered genetic nanomedicine. Four-component lipid nanoparticles (LNPs) consisting of ionizable lipids, phospholipids, cholesterol, and PEG-conjugated lipids, assembled by microfluidic or T-tube, are the benchmark synthetic vector for delivery of mRNA. One-component multifunctional sequence-defined ionizable amphiphilic Janus dendrimer (IAJD) delivery systems for mRNA were developed by us to complement LNPs. IAJDs consist of multifunctional hydrophilic low-generation dendrons or minidendrons conjugated to hydrophobic dendrons. They were inspired by amphiphilic Janus dendrimers and glycodendrimers. IAJDs coassemble with mRNA into predictable-size vesicles, named dendrimersome nanoparticles (DNPs), by simple injection in acetate buffer, rather than by the complex technology required by LNPs. Assembly of DNPs by simple injection together with sequence design in the hydrophilic and hydrophobic modules of IAJDs endowed rapid screening to access discovery. Molecular design principles for targeted delivery were elaborated when the branching points of IAJDs were constructed from symmetrically and nonsymmetrically substituted plant phenolic acids interconnected by pentaerythritol (PE). Here, we report the first library containing simplified IAJDs constructed in only three steps from symmetrically trialkylated PE in the hydrophobic domain and four different piperazine-based ionizable amines in the hydrophilic part. Rapid coassembly with mRNA and in vivo screening led to the discovery of the two most active IAJDs targeting the spleen, liver, and lymph nodes, one predominantly to the spleen and liver and six delivering equally to the spleen, liver, lung, and lymph nodes. These IAJDs represent the simplest synthetic vectors and the first viral or synthetic system delivering equally to multiple organs.

Screening Libraries to Discover Molecular Design Principles for the Targeted Delivery of mRNA with One-Component Ionizable Amphiphilic Janus Dendrimers Derived from Plant Phenolic Acids.

Viral and synthetic vectors to deliver nucleic acids were key to the rapid development of extraordinarily efficient COVID-19 vaccines. The four-component lipid nanoparticles (LNPs), containing phospholipids, PEG-conjugated lipids, cholesterol, and ionizable lipids, co-assembled with mRNA via a microfluidic technology, are the leading nonviral delivery vector used by BioNTech/Pfizer and Moderna to access COVID-19 mRNA vaccines. LNPs exhibit a statistical distribution of their four components when delivering mRNA. Here, we report a methodology that involves screening libraries to discover the molecular design principles required to realize organ-targeted mRNA delivery and mediate activity with a one-component ionizable multifunctional amphiphilic Janus dendrimer (IAJD) derived from plant phenolic acids. IAJDs co-assemble with mRNA into monodisperse dendrimersome nanoparticles (DNPs) with predictable dimensions, via the simple injection of their ethanol solution in a buffer. The precise location of the functional groups in one-component IAJDs demonstrated that the targeted organs, including the liver, spleen, lymph nodes, and lung, are selected based on the hydrophilic region, while activity is associated with the hydrophobic domain of IAJDs. These principles, and a mechanistic hypothesis to explain activity, simplify the synthesis of IAJDs, the assembly of DNPs, handling, and storage of vaccines, and reduce price, despite employing renewable plant starting materials. Using simple molecular design principles will lead to increased accessibility to a large diversity of mRNA-based vaccines and nanotherapeutics.

Assembling Complex Macromolecules and Self-Organizations of Biological Relevance with Cu(I)-Catalyzed Azide-Alkyne, Thio-Bromo, and TERMINI Double "Click" Reactions.

In 2022, the Nobel Prize in Chemistry was awarded to Bertozzi, Meldal, and Sharpless "for the development of click chemistry and biorthogonal chemistry". Since 2001, when the concept of click chemistry was advanced by Sharpless laboratory, synthetic chemists started to envision click reactions as the preferred choice of synthetic methodology employed to create new functions. This brief perspective will summarize research performed in our laboratories with the classic Cu(I)-catalyzed azide-alkyne click (CuAAC) reaction elaborated by Meldal and Sharpless, with the thio-bromo click (TBC) and with the less-used, irreversible TERminator Multifunctional INItiator (TERMINI) dual click (TBC) reactions, the last two elaborated in our laboratory. These click reactions will be used to assemble, by accelerated modular-orthogonal methodologies, complex macromolecules and self-organizations of biological relevance. Self-assembling amphiphilic Janus dendrimers and Janus glycodendrimers together with their biological membrane mimics known as dendrimersomes and glycodendrimersomes as well as simple methodologies to assemble macromolecules with perfect and complex architecture such as dendrimers from commercial monomers and building blocks will be discussed. This perspective is dedicated to the 75th anniversary of Professor Bogdan C. Simionescu, the son of my (VP) Ph.D. mentor, Professor Cristofor I. Simionescu, who as his father, took both science and science administration in his hands, and dedicated his life to handling them in a tandem way, to their best.

microRNAs associated with the pathogenesis and their role in regulating various signaling pathways during Mycobacterium tuberculosis infection.

Despite more than a decade of active study, tuberculosis (TB) remains a serious health concern across the world, and it is still the biggest cause of mortality in the human population. Pathogenic bacteria recognize host-induced responses and adapt to those hostile circumstances. This high level of adaptability necessitates a strong regulation of bacterial metabolic characteristics. Furthermore, the immune reponse of the host virulence factors such as host invasion, colonization, and survival must be properly coordinated by the pathogen. This can only be accomplished by close synchronization of gene expression. Understanding the molecular characteristics of mycobacterial pathogenesis in order to discover therapies that prevent or resolve illness relies on the bacterial capacity to adjust its metabolism and replication in response to various environmental cues as necessary. An extensive literature details the transcriptional alterations of host in response to in vitro environmental stressors, macrophage infection, and human illness. Various studies have recently revealed the finding of several microRNAs (miRNAs) that are believed to play an important role in the regulatory networks responsible for adaptability and virulence in Mycobacterium tuberculosis. We highlighted the growing data on the existence and quantity of several forms of miRNAs in the pathogenesis of M. tuberculosis, considered their possible relevance to disease etiology, and discussed how the miRNA-based signaling pathways regulate bacterial virulence factors.

Technology development to evaluate the effectiveness of viscosity reducing excipients.

Addition of pharmaceutical excipients is a commonly used approach to decrease the viscosity of highly concentrated protein formulations, which otherwise could not be subcutaneously injected or processed. The variety of protein-protein interactions, which are responsible for increased viscosities, makes a portfolio approach necessary. Screening of several excipients to develop such a portfolio is time and money consuming in industrial settings. Responsible protein-protein interactions were investigated using the interaction parameter kD obtained from dynamic light scattering measurements in the studies presented herein. Together with in-silico calculated excipient parameter, kD could be used as a screening tool accelerating screening and formulation development as kD is suitable to high-throughput formats using small quantities of protein and low concentrations. A qualitative correlation between kD and high-concentration viscosity behavior could be shown in our case.

SARS-CoV-2 seroprevalence in the city of Hyderabad, India in early 2021.

Background: COVID-19 emerged as a global pandemic in 2020, spreading rapidly to most parts of the world. The proportion of infected individuals in a population can be reliably estimated via serosurveillance, making it a valuable tool for planning control measures. Our serosurvey study aimed to investigate SARS-CoV-2 seroprevalence in the urban population of Hyderabad at the end of the first wave of infections. Methods: This cross-sectional survey, conducted in January 2021 and including males and females aged 10 years and above, used multi-stage random sampling. 9363 samples were collected from 30 wards distributed over six zones of Hyderabad, and tested for antibodies against SARS-CoV-2 nucleocapsid antigen. Results: Overall seropositivity was 54.2%, ranging from 50% to 60% in most wards. Highest exposure appeared to be among those aged 30-39 and 50-59 years, with women showing greater seropositivity. Seropositivity increased with family size, with only marginal differences among people with varying levels of education. Seroprevalence was significantly lower among smokers. Only 11% of the survey subjects reported any COVID-19 symptoms, while 17% had appeared for COVID-19 testing. Conclusion: Over half the city's population was infected within a year of onset of the pandemic. However, ∼ 46% of people remained susceptible, contributing to subsequent waves of infection.

Identification of mycobacterial MPT-64 and ESAT-6 proteins in urogenital tuberculosis patients by real-time immuno-PCR.

Aim: Diagnosis of urogenital tuberculosis (UGTB) is difficult and there is an immediate need to develop a reliable diagnostic test. Methods: A real-time immuno-PCR (RT-I-PCR) was developed to identify a cocktail of MPT-64 + ESAT-6 in both male/female UGTB patients comprising five confirmed cases, 40 clinically suspected cases and 37 non-TB controls, from whom mid-stream urine specimens were collected, while endometrial biopsies of female patients were obtained on day 1 of their menstrual cycle. Results obtained by RT-I-PCR were compared with I-PCR/ELISA and GeneXpert. Results: A wide range (500 fg/ml-10 ng/ml) of MPT-64 + ESAT-6 was detected in UGTB specimens by RT-I-PCR, although ELISA showed a narrow range (2.5-11 ng/ml). Sensitivities of 80% and 82.2% were obtained by RT-I-PCR in clinically suspected and total UGTB cases, respectively, whereas 94.6% specificity was obtained. Concurrently, RT-I-PCR revealed significantly higher (p < 0.05-0.001) sensitivity than I-PCR/ELISA and GeneXpert. Conclusion: After improving the specificity, the authors may develop RT-I-PCR into a diagnostic kit.

Urogenital tuberculosis (UGTB) involves infection of the urinary tract and genital organs of male/female patients by Mycobacterium tuberculosis bacteria. Delayed diagnosis and therapy of UGTB lead to infertility and kidney failure. The routine tests used to detect the bacteria are not very sensitive due to low levels of bacteria present in UGTB specimens. Moreover, most nucleic acid amplification tests, such as PCR tests, give false-positive and false-negative results. The authors designed a real-time immuno-PCR test for detecting a cocktail of M. tuberculosis proteins in UGTB patients that revealed quite promising results, which were superior to immuno-PCR/ELISA and GeneXpert tests. After further improvement in the specificity and reduction of the price, this real-time immuno-PCR test could be used in routine diagnosis.

The Unexpected Importance of the Primary Structure of the Hydrophobic Part of One-Component Ionizable Amphiphilic Janus Dendrimers in Targeted mRNA Delivery Activity.

Viral and synthetic vectors for delivery of nucleic acids impacted genetic nanomedicine by aiding the rapid development of the extraordinarily efficient Covid-19 vaccines. Access to targeted delivery of nucleic acids is expected to expand the field of nanomedicine beyond most expectations. Both viral and synthetic vectors have advantages and disadvantages. The major advantage of the synthetic vectors is their unlimited synthetic capability. The four-component lipid nanoparticles (LNPs) are the leading nonviral vector for mRNA used by Pfizer and Moderna in Covid-19 vaccines. Their synthetic capacity inspired us to develop a one-component multifunctional sequence-defined ionizable amphiphilic Janus dendrimer (IAJD) delivery system for mRNA. The first experiments on IAJDs provided, through a rational-library design combined with orthogonal-modular accelerated synthesis and sequence control in their hydrophilic part, some of the most active synthetic vectors for the delivery of mRNA to lung. The second experiments employed a similar strategy, generating, by a less complex hydrophilic structure, a library of IAJDs targeting spleen, liver, and lung. Here, we report preliminary studies designing the hydrophobic region of IAJDs by using dissimilar alkyl lengths and demonstrate the unexpectedly important role of the primary structure of the hydrophobic part of IAJDs by increasing up to 90.2-fold the activity of targeted delivery of mRNA to spleen, lymph nodes, liver, and lung. The principles of the design strategy reported here and in previous publications indicate that IAJDs could have a profound impact on the future of genetic nanomedicine.

Targeted Delivery of mRNA with One-Component Ionizable Amphiphilic Janus Dendrimers.

Targeted and efficient delivery of nucleic acids with viral and synthetic vectors is the key step of genetic nanomedicine. The four-component lipid nanoparticle synthetic delivery systems consisting of ionizable lipids, phospholipids, cholesterol, and a PEG-conjugated lipid, assembled by microfluidic or T-tube technology, have been extraordinarily successful for delivery of mRNA to provide Covid-19 vaccines. Recently, we reported a one-component multifunctional sequence-defined ionizable amphiphilic Janus dendrimer (IAJD) synthetic delivery system for mRNA relying on amphiphilic Janus dendrimers and glycodendrimers developed in our laboratory. Amphiphilic Janus dendrimers consist of functional hydrophilic dendrons conjugated to hydrophobic dendrons. Co-assembly of IAJDs with mRNA into dendrimersome nanoparticles (DNPs) occurs by simple injection in acetate buffer, rather than by microfluidic devices, and provides a very efficient system for delivery of mRNA to lung. Here we report the replacement of most of the hydrophilic fragment of the dendron from IAJDs, maintaining only its ionizable amine, while changing its interconnecting group to the hydrophobic dendron from amide to ester. The resulting IAJDs demonstrated that protonated ionizable amines play dual roles of hydrophilic fragment and binding ligand for mRNA, changing delivery from lung to spleen and/or liver. Replacing the interconnecting ester with the amide switched the delivery back to lung. Delivery predominantly to liver is favored by pairs of odd and even alkyl groups in the hydrophobic dendron. This simple structural change transformed the targeted delivery of mRNA mediated with IAJDs, from lung to liver and spleen, and expands the utility of DNPs from therapeutics to vaccines.

Catalyzing Bond-Dissociation in Graphene via Alkali-Iodide Molecules.

Atomic design of a 2D-material such as graphene can be substantially influenced by etching, deliberately induced in a transmission electron microscope. It is achieved primarily by overcoming the threshold energy for defect formation by controlling the kinetic energy and current density of the fast electrons. Recent studies have demonstrated that the presence of certain species of atoms can catalyze atomic bond dissociation processes under the electron beam by reducing their threshold energy. Most of the reported catalytic atom species are single atoms, which have strong interaction with single-layer graphene (SLG). Yet, no such behavior has been reported for molecular species. This work shows by experimentally comparing the interaction of alkali and halide species separately and conjointly with SLG, that in the presence of electron irradiation, etching of SLG is drastically enhanced by the simultaneous presence of alkali and iodine atoms. Density functional theory and first principles molecular dynamics calculations reveal that due to charge-transfer phenomena the CC bonds weaken close to the alkali-iodide species, which increases the carbon displacement cross-section. This study ascribes pronounced etching activity observed in SLG to the catalytic behavior of the alkali-iodide species in the presence of electron irradiation.

One-Component Multifunctional Sequence-Defined Ionizable Amphiphilic Janus Dendrimer Delivery Systems for mRNA.

Efficient viral or nonviral delivery of nucleic acids is the key step of genetic nanomedicine. Both viral and synthetic vectors have been successfully employed for genetic delivery with recent examples being DNA, adenoviral, and mRNA-based Covid-19 vaccines. Viral vectors can be target specific and very efficient but can also mediate severe immune response, cell toxicity, and mutations. Four-component lipid nanoparticles (LNPs) containing ionizable lipids, phospholipids, cholesterol for mechanical properties, and PEG-conjugated lipid for stability represent the current leading nonviral vectors for mRNA. However, the segregation of the neutral ionizable lipid as droplets in the core of the LNP, the "PEG dilemma", and the stability at only very low temperatures limit their efficiency. Here, we report the development of a one-component multifunctional ionizable amphiphilic Janus dendrimer (IAJD) delivery system for mRNA that exhibits high activity at a low concentration of ionizable amines organized in a sequence-defined arrangement. Six libraries containing 54 sequence-defined IAJDs were synthesized by an accelerated modular-orthogonal methodology and coassembled with mRNA into dendrimersome nanoparticles (DNPs) by a simple injection method rather than by the complex microfluidic technology often used for LNPs. Forty four (81%) showed activity in vitro and 31 (57%) in vivo. Some, exhibiting organ specificity, are stable at 5 °C and demonstrated higher transfection efficiency than positive control experiments in vitro and in vivo. Aside from practical applications, this proof of concept will help elucidate the mechanisms of packaging and release of mRNA from DNPs as a function of ionizable amine concentration, their sequence, and constitutional isomerism of IAJDs.

SARS-CoV-2 seroprevalence in the city of Hyderabad, India in early 2021

BackgroundCOVID-19 emerged as a global pandemic in 2020, rapidly spreading to most parts of the world. The proportion of infected individuals in a population can be reliably estimated via sero-surveillance, making it a valuable tool for planning control measures. We conducted a serosurvey study to investigate SARS-CoV-2 seroprevalence in the urban population of Hyderabad at the end of the first wave of infections. MethodsThe cross-sectional survey conducted in January 2021 included males and females aged 10 years and above, selected by multi-stage random sampling. 9363 samples were collected from 30 wards distributed over 6 zones of Hyderabad and tested for antibodies against SARS-CoV-2 nucleocapsid antigen. ResultsOverall seropositivity was 54.2%, ranging from 50-60% in most wards. Highest exposure appeared to be among 30-39y and 50-59y olds, with women showing greater seropositivity. Seropositivity increased with family size, with only marginal differences among people with varying levels of education. Seroprevalence was significantly lower among smokers. Only 11% of the survey subjects reported any COVID-19 symptoms, while 17% had appeared for Covid testing. ConclusionOver half the citys population was infected within a year of onset of the pandemic. However, [~]46% people were still susceptible, contributing to subsequent waves of infection. Highlights National level serosurveys under-estimate localised prevalence in dense urban areas SARS-CoV-2 seroprevalence in Hyderabad city was 54.2% after the first wave A large proportion of the population remains at risk over a year into the pandemic

Barbiturate derivatives for managing multifaceted oncogenic pathways: A mini review.

Development and progression of metastasis comprises synchronized erroneous expressions of several composite pathways, which are difficult to manage simultaneously with the representative anticancer molecules. The emergence of the drug resistance and the complex interplay between these pathways further potentiates cancer related complexities. Barbiturates and their derivatives present a commendable anticancer profile by attenuating the cancer manifesting metabolic and enzymatic pathways including, but not limited to matrix metalloproteinases, xanthine oxidase, amino peptidases, histone deacetylases, and Ras/mitogen-activated protein kinase. The derivatization and conjugation of barbiturates with pharmacophores delivers a suitable hybrid profile in containing the anomalous expression of these pathways. The present report presents a succinct collation of the barbiturates and their derivatives in managing the various cancer causing pathways.

The initial experience of 2495 cases of the ulnar artery as default access for coronary diagnostic and interventional procedures at a single center: An observational study.

INTRODUCTION: Upper limb arterial access is being increasingly used for coronary diagnostic and intervention procedures. Radial artery access is associated with reduced morbidity and mortality as compared to femoral artery access. However, access to the radial artery is not always successful with reported crossover rates to other routes between 3% and 8%. Ulnar artery access is emerging an attractive option both as upfront access and rescue access in case of failure to obtain radial artery access. AIMS -: To assess and document the feasibility and safety of ulnar access as a default strategy. METHODS: 2654 patients planned for coronary diagnostic and intervention procedureswere assessed for inclusion. Inclusion criteria were, all patients planned for coronary angiography (CAG) or percutaneous coronary intervention (PCI) with palpable ulnar pulse. Exclusion criteria included reverse Barbeau test type D, previous procedure resulting in radial artery occlusion/excision, hemodialysis patients having ipsilateral AV fistula and severe forearm deformities. RESULTS: 2525 patients were found eligible, out of which 2495 (98.81%) were successfully cannulated. Procedure was completed in 2414 patients. Local site bleeding in 40 (1.6%) and acute loss of ulnar pulse noted in 33 (1.3%) out of 2495 patients. None of the patients had gangrene of access site, pseudo-aneurysm, arteriovenous fistula or neurological deficit post procedure. CONCLUSION: The Ulnar artery access as a default access is safe and feasible option for patient undergoing coronary diagnostic and interventional procedures.

Me6-TREN/TREN Mixed-Ligand Effect During SET-LRP in the Catalytically Active DMSO Revitalizes TREN into an Excellent Ligand.

A mixed-ligand effect was observed for mixtures of tris(2-dimethylaminoethyl)amine (Me6-TREN) with tris(2-aminoethyl)amine (TREN) ligands during Cu(0) wire-catalyzed, single-electron transfer-living radical polymerization (SET-LRP) of methyl acrylate (MA) initiated with bis(2-bromopropionyl)ethane (BPE) in DMSO. The external order of reaction of SET-LRP both in the presence of Me6-TREN, TREN and of the mixed-ligand Me6-TREN/TREN, in DMSO, demonstrated a catalytic activity for DMSO similar to that reported in the presence of Cu(0) powder. The catalytic activity of DMSO, with close to 100% chain-end functionality, facilitates the much less expensive TREN to act as a very efficient ligand that is competitive with Me6-TREN and with the mixed-ligand and revitalizes TREN into an excellent ligand. The highest activity of the mixed-ligand at 1/1 ratio between ligands suggests that in addition to a fast exchange between these two ligands, a new single dynamic ligand stabilized by hydrogen-bonding, may generate these results.

Replacing Cu(II)Br2 with Me6-TREN in Biphasic Cu(0)/TREN Catalyzed SET-LRP Reveals the Mixed-Ligand Effect.

The mixed-ligand system consisting of tris(2-aminoethyl)amine (TREN) and tris(2-dimethylaminoethyl)amine (Me6-TREN) during the Cu(0) wire-catalyzed single electron transfer-living radical polymerization (SET-LRP) of methyl acrylate (MA) in "programmed" biphasic mixtures of the dipolar aprotic solvents NMP, DMF, and DMAc with H2O is reported. Kinetic and chain end analysis studies by NMR and MALDI-TOF before and after thio-bromo "click" reaction demonstrated that Me6-TREN complements and makes the less expensive TREN a very efficient ligand in the absence of externally added Cu(II)Br2. Statistical analysis of the kinetic data together with control experiments demonstrated that this mixed-ligand effect enhanced the apparent rate constant of propagation, monomer conversion, and molecular weight control. The most efficient effect was observed at a 1/1 molar ratio between these two ligands, suggesting that in addition to a fast exchange between the two ligands, a new single dynamic ligand generated by hydrogen bonding may be responsible for the mixed ligand observed.