Copolymer Micelles Research Articles

Dendritic-Linear Copolymer and Dendron Lipid Nanoparticles for Drug and Gene Delivery.

Polymers constitute a diverse class of macromolecules that have demonstrated their unique advantages to be utilized for drug or gene delivery applications. In particular, polymers with a highly ordered, hyperbranched structure─"dendrons"─offer significant benefits to the design of such nanomedicines. The incorporation of dendrons into block copolymer micelles can endow various unique properties that are not typically observed from linear polymer counterparts. Specifically, the dendritic structure induces the conical shape of unimers that form micelles, thereby improving the thermodynamic stability and achieving a low critical micelle concentration (CMC). Furthermore, through a high density of highly ordered functional groups, dendrons can enhance gene complexation, drug loading, and stimuli-responsive behavior. In addition, outward-branching dendrons can support a high density of nonfouling polymers, such as poly(ethylene glycol), for serum stability and variable densities of multifunctional groups for multivalent cellular targeting and interactions. In this paper, we review the design considerations for dendron-lipid nanoparticles and dendron micelles formed from amphiphilic block copolymers intended for gene transfection and cancer drug delivery applications. These technologies are early in preclinical development and, as with other nanomedicines, face many obstacles on the way to clinical adoption. Nevertheless, the utility of dendron micelles for drug delivery remains relatively underexplored, and we believe there are significant and dramatic advancements to be made in tumor targeting with these platforms.

Natural and Synthetic Micelles for the Delivery of Small Molecule Drugs, Imaging Agents and Nucleic Acids.

The poor solubility, lack of targetability, quick renal clearance, and degradability of many therapeutic and imaging agents strongly limit their applications inside the human body. Amphiphilic copolymers having self-assembling properties can form core-shell structures called micelles, a promising nanocarrier for hydrophobic drugs, plasmid DNA, oligonucleotides, small interfering RNAs (siRNAs), and imaging agents. Fabrication of micelles loaded with different pharmaceutical agents provides numerous advantages, including therapeutic efficacy, diagnostic sensitivity, and controlled release to the desired tissues. Moreover, their smaller particle size (10-100 nm) and modified surfaces with different functional groups (such as ligands) help them to accumulate easily in the target location, enhancing cellular uptake and reducing unwanted side effects. Furthermore, the release of the encapsulated agents may also be triggered from stimuli-sensitive micelles under different physiological conditions or by an external stimulus. In this review article, we discuss the recent advancements in formulating and targeting of different natural and synthetic micelles, including block copolymer micelles, cationic micelles, and dendrimers-, polysaccharide- and protein-based micelles for the delivery of different therapeutic and diagnostic agents. Finally, their applications, outcomes, and future perspectives have been summarized.

Biocompatibility and Physiological Thiolytic Degradability of Radically Made Thioester-Functional Copolymers: Opportunities for Drug Release.

Being nondegradable, vinyl polymers have limited biomedical applicability. Unfortunately, backbone esters incorporated through conventional radical ring-opening methods do not undergo appreciable abiotic hydrolysis under physiologically relevant conditions. Here, PEG acrylate and di(ethylene glycol) acrylamide-based copolymers containing backbone thioesters were prepared through the radical ring-opening copolymerization of the thionolactone dibenzo[c,e]oxepin-5(7H)-thione. The thioesters degraded fully in the presence of 10 mM cysteine at pH 7.4, with the mechanism presumed to involve an irreversible S–N switch. Degradations with N-acetylcysteine and glutathione were reversible through the thiol–thioester exchange polycondensation of R–SC(=O)–polymer–SH fragments with full degradation relying on an increased thiolate/thioester ratio. Treatment with 10 mM glutathione at pH 7.2 (mimicking intracellular conditions) triggered an insoluble–soluble switch of a temperature-responsive copolymer at 37 °C and the release of encapsulated Nile Red (as a drug model) from core-degradable diblock copolymer micelles. Copolymers and their cysteinolytic degradation products were found to be noncytotoxic, making thioester backbone-functional polymers promising for drug delivery applications.

Recent advances in the synthesis and applications of pH-responsive CaCO3

The biocompatible calcium carbonate (CaCO3) dissociates at low pH, making it a safe pH-responsive building block. Many synthesis routes have been introduced to build CaCO3 based pH-responsive solutions, but there is a lack of detailed comparison. This review aims to compare synthesis routes and applications of pH-responsive CaCO3 based drug delivery systems, nondrug delivery systems, imaging techniques, sensors, and templates. The novelty and limitations in each synthesis and application were successfully identified. CaCO3 based drug delivery systems were extensively developed through impregnation or encapsulation for cancer treatment. The polymer coatings reduced burst release, while metal doping promoted therapeutic effects. Fe2O3 nanoparticles with magnetic properties could initiate Fenton reactions for destroying mitochondrial. Alginate further controlled drug loading and release, allowing dissociation at the reduced condition in the presence of glutathione. Poly(ethylene glycol) delayed release at low pH, and its copolymer micelles are the effective template to build CaCO3 drug delivery systems. Cholesterol-lowering drugs, insulin, and other biocompounds were also loaded into CaCO3 delivery systems. Due to the generation of carbon dioxide, ultrasound imaging could be enhanced. The release of Ca2+ ions triggered the alginate gelation, which enhances photoluminescent changes or electron transfer in sensors. CaCO3 was also utilized as the scarifying template in the drug delivery systems. Past works inspire more uses of CaCO3 for developing pH-responsive concrete, adsorbents, and membranes.

PLA-PEG Diblock Copolymer Micelle as Nanocarrier for Anti-Obesity Drug Delivery System

Obesity is a metabolic condition that accounts for life-threatening disorders like cancer, cardiovascular diseases, and type 2 diabetes. There are several anti-obesity drugs currently available on the market, but many of them show poor bioavailability due to low water solubility. Several attempts have been made by researchers to improve the solubility of orally administered drugs, but many of them did not work properly. Herein, we introduced a block copolymer micelle consisting of poly (lactic acid)-co-poly (ethylene glycol) to improve the solubility of the anti-obesity drug "Fenofibrate.” The block copolymer was synthesized using the polycondensation method, while the micelle was formed when water was added dropwise to the copolymer. Finally, laser light scattering and DLS analysis were used to confirm the micelle formation. The size of the micelle increased from 158 nm to 249 nm after the fenofibrate drug loading inside the hydrophobic core. The polymer PLA-co-PEG can be used as a carrier for orally administered fenofibrate drugs in the future for better water solubility and efficiency.

Assembly of Semiconductor Nanorods into Circular Arrangements Mediated by Block Copolymer Micelles.

The collective properties of ordered ensembles of anisotropically shaped nanoparticles depend on the morphology of organization. Here, we describe the utilization of block copolymer micelles to bias the natural packing tendency of semiconductor nanorods and organize them into circularly arranged superstructures. These structures are formed as a result of competition between the segregation tendency of the nanorods in solution and in the polymer melt; when the nanorods are highly compatible with the solvent but prefer to segregate in the melt to the core-forming block, they migrate during annealing toward the core–corona interface, and their superstructure is, thus, templated by the shape of the micelle. The nanorods, in turn, exhibit surfactant-like behavior and protect the micelles from coalescence during annealing. Lastly, the influence of the attributes of the micelles on nanorod organization is also studied. The circular nanorod arrangements and the insights gained in this study add to a growing list of possibilities for organizing metal and semiconductor nanorods that can be achieved using rational design.

Vitamin A - modified Betulin polymer micelles with hepatic targeting capability for hepatic fibrosis protection

Targeting hepatic stellate cells (HSCs) can improve the therapeutic efficacy of medicines used to treat hepatic fibrosis. The present work aimed to study the feasibility of homing devices with vitamin A(VA) chemically attached for delivering betulin(Bt)specifically to HSCs. The manufacture and characterisation of VA modified poly (ethylene glycol) -poly (lactide-co-glycolide) block copolymer micelles loaded with Bt (Bt/ VAPPMs) and their potential therapeutic benefits in vitro and in vivo are described in this paper. Bt/VAPPMs were made in a nearly spherical core-shell configuration with diameters under 200nm.In vitro release study showed that Bt/VAPPMs exhibited steady and continuous release for over 168 hours. Bt/VAPPMs had good biocompatibility at the cellular level, according to the safety evaluation, and elicited no inflammatory response in mice. More importantly, as uptake behavior studied in cells and bioimaging experiments in vivo, Bt/VAPPMs exhibited an instinctive liver- targeting capability to focus on activated HSCs. Efficacy tests revealed that administering Bt/VAPPMs effectively inhibits collagen I expression in LX-2 cells in vitro, and this effect was also seen in a mouse model of liver fibrosis. Overall, results demonstrated that Bt/VAPPMs is a promising drug delivery system that possesses specific HSCs targeting ability for treating hepatic fibrosis.

Interfacial Rearrangements of Block Copolymer Micelles Toward Gelled Liquid-Liquid Interfaces with Adjustable Viscoelasticity.

Though amphiphiles are ubiquitously used for altering interfaces, interfacial reorganization processes are in many cases obscure. For example, adsorption of micelles to liquid-liquid interfaces is often accompanied by rapid reorganizations toward monolayers. Then, the involved time scales are too short to be followed accurately. A block copolymer system, which comprises poly(ethylene oxide)110 -b-poly{[2-(methacryloyloxy)ethyl]diisopropylmethylammonium chloride}170 (i.e., PEO110 -b-qPDPAEMA170 with quaternized poly(diisopropylaminoethyl methacrylate)) is presented. Its reorganization kinetics at the water/n-decane interface is slowed down by electrostatic interactions with ferricyanide ([Fe(CN)6 ]3- ). This deceleration allows an observation of the restructuring of the adsorbed micelles not only by tracing the interfacial pressure, but also by analyzing the interfacial rheology and structure with help of atomic force microscopy. The observed micellar flattening and subsequent merging toward a physically interconnected monolayer lead to a viscoelastic interface well detectable by interfacial shear rheology (ISR). Furthermore, the "gelled" interface is redox-active, enabling a return to purely viscous interfaces and hence a manipulation of the rheological properties by redox reactions. Additionally, interfacial Prussian blue formation stiffens the interface. Such manipulation and in-depth knowledge of the rheology of complex interfaces can be beneficial for the development of emulsion formulations in industry or medicine, where colloidal stability or adapted permeability is crucial.

A Radiolabeling Method for Precise Quantification of Polymers

Radiolabeling a protein, molecule, or polymer can provide accurate and precise quantification in biochemistry, biomaterials, pharmacology, and drug delivery research. Herein, we describe a method to 125I label two different polymers for precise quantification in different applications. The surfaces of model contact lenses were modified with phenylboronic acid to bind and release the natural polymer, hyaluronic acid (HA); HA uptake and release were quantified by radiolabeling. In the second example, the in vivo distribution of a mucoadhesive micelle composed of the block copolymer of poly(lactide)-b-poly(methacrylic acid-co-acrylamidophenylboronic acid) was investigated. The presence of phenyl boronic acid groups (PBA), which bind to mucosal surfaces, was proposed to improve the retention of the micelle. 125I labeling of polymers was examined for quantification of microgram amounts of HA present on a contact lens or to evaluate the enhanced retention of PBA micelles on mucosal surfaces in vivo. The introduction of phenol groups onto the polymers allowed for the labeling. HA was modified with phenol groups through a coupling reaction of its carboxylic acid with hydroxybenzylamine. Phenol functional block copolymer micelles with and without PBA were synthesized by including N-(4-hydroxyphenethyl)acrylamide during polymerization. The phenol groups of HA and the block copolymers were labeled with 125I using a modified ICl labeling method. 125I labeling enabled quantification of HA loading and release including the effect of varying amounts of PBA on the contact lens surfaces. Micelles made from 125I-labeled block copolymers with and without PBA were administered intranasally to Brown Norway rats. The animals were sacrificed either immediately after or 4 h after their last nasal instillation, and the nasopharyngeal tissues were removed and quantified. Radioactivity measurements demonstrated that the presence of the PBA mucosal binding groups led to approximately four times higher retention. The HA and block copolymer 125I labeling presented in this article demonstrates the utility of the method for quantification and tracking of microgram quantities of polymers in diverse applications.

Frontispiece: Self‐Assembled Fluorescent Block Copolymer Micelles with Responsive Emission

Polymer Micelles Self-assembled fluorescent block copolymer micelles with responsive emission are reported by Birgit Weber et al. in their Research Article (e202117570).

"Self-Adaptive" Coassembly of Colloidal "Saturn-like" Host-Guest Complexes Enabled by Toroidal Micellar Rubber Bands.

The creation of inclusion complexes with "Saturn-like" geometries has attracted increasing attention for supramolecular systems, but expansion of the concept to nanoscale colloidal systems remains a challenge. Here, we report a strategy to assemble toroidal polyisoprene-b-poly(2-vinylpyridine) (PI-b-P2VP) block copolymer micelles with a PI core and a P2VP corona and inorganic (e.g., silica) nanoparticles of variable shape and dimensions into "Saturn-like" constructs with high fidelity and yield. The precise nesting of the nanoparticles between the toroidal building units is realized by virtue of hydrogen bonding and self-adaptive expansion of the flexible toroidal units enabled by a flexible, low Tg PI core. Once the toroidal units are cross-linked, the self-adaptive feature is lost and coassembly yields instead out-of-cavity bound nanoparticles. "Saturn-like" assemblies can also be formed along silica nanosphere-decorated cylindrical micelles or, alternatively, at the hydroxyl-functionalized termini of cylindrical micelles to yield colloidal [3]rotaxanes.

Microfluidic Synthesis of Block Copolymer Micelles: Application as Drug Nanocarriers and as Photothermal Transductors When Loading Pd Nanosheets.

The synthesis of polymeric nanoparticles from a block copolymer based on poly(ethylene glycol) and a polymethacrylate containing the nucleobase analog 2,6-diacylaminopyridine is optimized by microfluidics to obtain homogeneous spherical micelles. Loading and delivery properties are studied using naproxen as a model. The incorporation of a Pd precursor in the polymer organic solution fed into the micromixer allows the preparation of Pd(II) precursor-polymer hybrid systems and the subsequent reduction with CO leads to the in situ synthesis of Pd nanosheets inside of the hydrophobic core of the polymeric micelles. This methodology is highly efficient to yield all polymeric nanoparticles loaded with Pd nanosheets as detected by electron microscopy and energy-dispersive X-ray spectroscopy. The cell viability of these Pd nanosheets-containing polymeric nanoparticles is evaluated using five cell lines, showing a high cytocompatibility at the tested concentrations without detrimental effects in cell membrane and nuclei. Furthermore, the use of these hybrid polymeric nanoparticles as photothermal transductors is evaluated using near infrared as irradiation source as well as its application in photothermal therapy using different cell lines demonstrating a high efficiency in all cell cultures.

Self-Assembled Fluorescent Block Copolymer Micelles with Responsive Emission.

Responsive fluorescent materials offer a high potential for sensing and (bio‐)imaging applications. To investigate new concepts for such materials and to broaden their applicability, the previously reported non‐fluorescent zinc(II) complex [Zn(L)] that shows coordination‐induced turn‐on emission was encapsulated into a family of non‐fluorescent polystyrene‐block‐poly(4‐vinylpyridine) (PS‐b‐P4VP) diblock copolymer micelles leading to brightly emissive materials. Coordination‐induced turn‐on emission upon incorporation and ligation of the [Zn(L)] in the P4VP core outperform parent [Zn(L)] in pyridine solution with respect to lifetimes, quantum yields, and temperature resistance. The quantum yield can be easily tuned by tailoring the selectivity of the employed solvent or solvent mixture and, thus, the tendency of the PS‐b‐P4VP diblock copolymers to self‐assemble into micelles. A medium‐dependent off–on sensor upon micelle formation could be established by suppression of non‐micelle‐borne emission background pertinent to chloroform through controlled acidification indicating an additional pH‐dependent process.

Selbstassemblierte fluoreszierende Blockcopolymer‐Mizellen mit responsiver Emission

Responsive, fluoreszierende Materialien versprechen neue Anwendungen in der Sensorik und der (biologischen) Bildgebung. In dieser Studie stellen wir einen konzeptionell neuartigen Zugang zu solchen Materialien auf Basis der Selbstassemblierung von nicht-fluoreszierenden Bausteinen zu fluoreszierenden Materialien vor. Stark emittierende Kompositmaterialien werden nach Verkapselung des nicht-fluoreszierenden Zink(II)-Komplexes [Zn(L)] in eine Reihe von nicht-fluoreszierenden Polystyrol-block-Poly(4-vinylpyridin) (PS-b-P4VP) Diblockcopolymer-Mizellen erhalten. Die koordinationsinduzierte Turn-On Emission von [Zn(L)] im P4VP-Kern übertrifft die von gelösten [Zn(L)] in Pyridin hinsichtlich wichtiger Gütefaktoren, wie Lebensdauer, Quantenausbeute und Temperaturbeständigkeit. Die Quantenausbeute kann leicht über das Medium eingestellt werden, indem die Tendenz der PS-b-P4VP Diblockcopolymere zur Selbstassemblierung zu Mizellen über die Selektivität des verwendeten Lösungsmittels oder Lösungsmittelgemisches angepasst wird. Ein medienabhängiger Off-On Sensor, der mit der Mizellbildung gekoppelt ist, konnte durch Unterdrückung des nicht mizellenbasierten Emissionshintergrunds in Chloroform durch kontrolliertes Ansäuern realisiert werden, was auf einen zusätzlichen pH-abhängigen Prozess hinweist.

Polymeric Surfactant P84/Polyoxometalate α-PW12O403−—A Model System to Investigate the Interplay between Chaotropic and Hydrophobic Effects

Low charge density nanometric ions were recently shown to bind strongly to neutral hydrated matter in aqueous solution. This phenomenon, called the (super-)chaotropic effect, arises from the partial dehydration of both the nano-ion and the solute, leading to a significant gain in enthalpy. Here, we investigate the chaotropic effect of the polyoxometalate α-PW12O403− on the triblock copolymer P84: (EO)19(PO)43(EO)19 with (EO)19 the polyethoxylated and (PO)43 the polypropoxylated chains. The combination of phase diagrams, spectroscopic (nuclear magnetic resonance) and scattering (small angle neutron/X-ray scattering) techniques revealed that: (i) below the micellization temperature of P84, PW12O403− exclusively binds to the propylene oxide moiety of P84 unimers; and (ii) above the micellization temperature, PW12O403− mostly adsorbs on the ethylene oxide micellar corona. The preferential binding of the PW12O403− to the PPO chain over the PEO chains suggests that the binding is driven by the chaotropic effect and is reinforced by the hydrophobic effect. At higher temperatures, copolymer micellization leads to the displacement of PW12O403− from the PPO chain to the PEO chains. This study deepens our understanding of the subtle interplay between the chaotropic and hydrophobic effects in complex salt-organic matter solutions.

Patch formation on diblock copolymer micelles confined in templates for inducing patch orientation and cyclic colloidal molecules

HypothesisChemically or physically distinct patches can be induced on the micelles of amphiphilic block copolymers, which facilitate directional binding for the creation of hierarchical structures. Hence, control over the direction of patches on the micelles is a crucial factor to attain the directionality on the interactions between the micelles, particularly for generating colloidal molecules mimicking the symmetry of molecular structures. We hypothesized that direction and combination of the patches could be controlled by physical confinement of the micelles. ExperimentsWe first confined spherical micelles of diblock copolymers in topographic templates fabricated from nanopatterns of block copolymers by adjusting the coating conditions. Then, patch formation was conducted on the confined micelles by exposing them with a core-favorable solvent. Microscopic techniques of SEM, TEM, and AFM were employed to investigate directions of patches and structures of combined micelles in the template. FindingsThe orientation of the patches on the micelles was guided by the physical confinement of the micelles in linear trenches. In addition, by confining the micelles in a circular hole, we obtained a specific polygon arrangement of the micelles depending on the number of micelles in the hole, which enabled the formation of cyclic colloidal molecules consisting of micelles.

Influence of Chain Length of Gradient and Block Copoly(2-oxazoline)s on Self-Assembly and Drug Encapsulation.

Amphiphilic gradient copolymers represent a promising alternative to extensively used block copolymers due to their facile one-step synthesis by statistical copolymerization of monomers of different reactivity. Herein, an in-depth analysis is provided of micelles based on amphiphilic gradient poly(2-oxazoline)s with different chain lengths to evaluate their potential for micellar drug delivery systems and compare them to the analogous diblock copolymer micelles. Size, morphology, and stability of self-assembled nanoparticles, loading of hydrophobic drug curcumin, as well as cytotoxicities of the prepared nanoformulations are examined using copoly(2-oxazoline)s with varying chain lengths and comonomer ratios. In addition to several interesting differences between the two copolymer architecture classes, such as more compact self-assembled structures with faster exchange dynamics for the gradient copolymers, it is concluded that gradient copolymers provide stable curcumin nanoformulations with comparable drug loadings to block copolymer systems and benefit from more straightforward copolymer synthesis. The study demonstrates the potential of amphiphilic gradient copolymers as a versatile platform for the synthesis of new polymer therapeutics.

Copolymer Micelle-administered Melatonin Ameliorates Hyperosmolarity-induced Ocular Surface Damage through Regulating PINK1-mediated Mitophagy

PurposeTo investigate the role and mechanism of melatonin-loaded polymer polyvinyl caprolactam–polyvinyl acetate–polyethyleneglycol graft copolymer micelles (Mel-Mic) in dry eye disease (DED).MethodsIn vitro, the apoptosis and reactive oxygen species (ROS) generation in human corneal epithelial cells (HCECs) were analyzed by immunostaining and flow cytometry. The effect of Mel-Mic on autophagy and mitophagy was evaluated by immunostaining and western blots. PINK1 knockdown was analyzed by small interfering RNA. In vivo, sodium fluorescein staining, tear secretion test, and periodic acid-Schiff staining were used to determine whether Mel-Mic can alleviate the severity of DED. Small molecule antagonists were pretreated to investigate whether melatonin type 1 and/or 2 receptors (MT1/MT2) mediate the effects of Mel-Mic.ResultsMel-Mic improved the solubility and biological activities of Mel in aqueous solutions. Treatment with Mel-Mic decreased the apoptosis of HCECs exposed to hyperosmotic medium, accompanied by downregulation of cleaved Caspase-3 and upregulation of Bcl-2. In addition, Mel-Mic application suppressed ROS overproduction, rescued mitochondrial function, and decreased the level of oxidative stress associated biomarkers (COX-2 and 4-HNE) in HCECs. Interestingly, HCECs treated with Mel-Mic exhibited increased levels of mitophagy markers (PINK1, PARKIN, Beclin 1, and LC3B) and restored impaired mitophagic flux under hyperosmolarity. While PINK1 knockdown largely abolished its protective effects. In vivo, compared to vehicle group, topical Mel-Mic-solution-treated mice showed significantly improved clinical parameters, increased tear production, and decreased goblet cells loss in a dose-dependent manner. Also, transmission electron microscopic assay revealed increased autophagosome number in the corneal epithelium of Mel-Mic group. Moreover, luzindole, a nonselective MT1/MT2 antagonist, but not 4-P-PDOT, a selective MT2 antagonist, blocked the protective effect of Mel-Mic.ConclusionsOur findings demonstrated that Mel-Mic ameliorates hyperosmolarity-induced ocular surface damage via PINK1-mediated mitophagy and may represent an effective treatment for DED possibly through acting MT1 receptor.

Modulating Boronic Ester Stability in Block Copolymer Micelles via the Neighbor Effect of Copolymerized Tertiary Amines for Controlled Release of Polyphenolic Drugs.

The traceless and pH-sensitive properties of boronic esters are attractive for the synthesis of polymer-drug conjugates, but current platforms suffer from both low stability under physiologically relevant conditions and synthetically demanding optimization to tune drug release profiles. We hypothesized that the high catechol affinity and stability of Wulff-type boronic acids could be mimicked by copolymerization of phenyl boronic acid with a tertiary amine and subsequent micellization. This strategy yielded a versatile platform for the preparation of reversible polymer-drug conjugates, which more than doubled the oxidative stability of encapsulated polyphenolic drug cargo at physiologically relevant pH and enabled simple and incremental tuning of drug release kinetics. Moreover, we validated, with 19F NMR, that these copolymers exhibit uniquely high catechol affinity that could not be replicated by combinations of similarly functionalized small molecules. Overall, this report demonstrates that copolymerization of boronic acid and tertiary amine monomers is a powerful and modular approach to improving boronic ester chemistry for drug delivery applications.

Structure of micelleplexes formed between QPDMAEMA-b-PLMA amphiphilic cationic copolymer micelles and DNA of different lengths

We study the structures of micelleplexes formed by quaternized poly(2-(dimethylamino) ethyl methacrylate)-b-poly(lauryl methacrylate) (QPDMAEMA-b-PLMA) amphiphilic cationic copolymer micelles interacting electrostatically with linear DNA of different lengths (113 and 2000 base pairs). QPDMAEMA-b-PLMA copolymers form micelles in aqueous milieu, with PLMA hydrophobic cores and QPDMAEMA cationic coronas. Nanosized micelleplexes were formed after mixing QPDMAEMA-b-PLMA micelles with DNAs, in a wide range of N/P ratios (nitrogen (N) of amine group of QPDMAEMA over phosphate (P) groups of DNA), as shown by Ultraviolet–Visible (UV–Vis) and fluorescence spectroscopy. Light scattering techniques demonstrated the formation of well-defined micelleplexes with monomodal and narrow size distributions, whose size and surface charge vary according to the N/P ratio. Micelleplexes presented stability under certain salt concentration. Spherical and worm-like micelleplexes were visualized by cryogenic transmission electron microscopy (Cryo-TEM). Overall, QPMDAEMA-b-PLMA micelles can efficiently interact with DNA. The stability, morphology and complexation of the micelleplexes were found to depend on copolymer molecular mass, the hydrophilic/hydrophobic ratio, the micellar structure, the length of DNA, the N/P ratio and the ionic strength. The findings demonstrate that QPDMAEMA-b-PLMA polyelectrolyte copolymer micelles have prospects for their application as non-viral vectors for nucleic acids delivery and gene therapy.