Flow-Driven Translocation of Strung Micelles Formed by Core–Shell Bottle-Brush Copolymers and the Accompanying Morphological Transformation through a Nanochannel

Herein, the flow-driven translocation of strung micelles formed by core–shell bottle-brush copolymers was investigated through hybrid lattice-Boltzmann molecular dynamics simulations. Results reveal that despite the submicelle size in two uniformly strung micelles being approximately the same as that of a single micelle, they exhibited a higher critical flow flux. Furthermore, two nonuniformly strung micelles exhibited a slightly higher critical flow flux compared to two uniformly strung micelles, which is mainly determined by the larger submicelle. Interestingly, most strung micelles transformed into cylindrical micelles after they crossed the nanochannel. These cylindrical micelles exhibited a lower critical flow flux compared with strung micelles because they were thinner than equivalent strung micelles. This study clarifies the transformations between various micelle structures during flow-driven translocation, emphasizing that spherical and cylindrical micelles are more easily generated when subjected to the constraints of a nanochannel. Additionally, it provides insights into the stability of strung micelles, contributing to the valuation of different micelle performances

Flow-Driven Translocation of Strung Micelles Formed by Core–Shell Bottle-Brush Copolymers and the Accompanying Morphological Transformation through a Nanochannel

Herein, the flow-driven translocation of strung micelles formed by core–shell bottle-brush copolymers was investigated through hybrid lattice-Boltzmann molecular dynamics simulations. Results reveal that despite the submicelle size in two uniformly strung micelles being approximately the same as that of a single micelle, they exhibited a higher critical flow flux. Furthermore, two nonuniformly strung micelles exhibited a slightly higher critical flow flux compared to two uniformly strung micelles, which is mainly determined by the larger submicelle. Interestingly, most strung micelles transformed into cylindrical micelles after they crossed the nanochannel. These cylindrical micelles exhibited a lower critical flow flux compared with strung micelles because they were thinner than equivalent strung micelles. This study clarifies the transformations between various micelle structures during flow-driven translocation, emphasizing that spherical and cylindrical micelles are more easily generated when subjected to the constraints of a nanochannel. Additionally, it provides insights into the stability of strung micelles, contributing to the valuation of different micelle performances

Molecular Dynamics Simulation of Salt Diffusion in Polyelectrolyte Assemblies

The diffusion of salt ions and charged probe molecules in polyelectrolyte (PE) assemblies is often assumed to follow a theoretical hopping model, in which the diffusing ion hops between charged sites of chains based on electroneutrality. However, experimental verification of diffusing pathway at such microscales is difficult, and the corresponding molecular mechanisms remain elusive. In this study, we perform all-atom molecular dynamics simulations of salt diffusion in the PE assembly of poly­(sodium-4-styrenesulfonate) (PSS) and poly­(diallyldimethylammonium chloride) (PDAC). Besides the ion hopping mode, the diffusing trajectories are found to present common features of a jump process, that is, subjecting to PE relaxation, water pockets in the structure open and close; thus, the ion can move from one pocket to another. Anomalous subdiffusion of ions and water is observed because of the trapping scenarios in these water pockets. The jump events are much rarer compared with ion hopping but significantly increases salt diffusion with increasing temperature. Our result strongly indicates that salt diffusion in hydrated PDAC/PSS is a combined process of ion hopping and jump motion. This provides a new molecular explanation for the coupling of salt motion with chain motion and the nonlinear increase of salt diffusion at glass-transition temperature

An Approach for the Sphere-to-Rod Transition of Multiblock Copolymer Micelles

The shape of polymer micelles is important for pharmaceutical applications as drug delivery. In this article, an approach inducing sphere-to-rod transition of multiblock polyurethane micelles has been developed through introducing a second hydrophilic component phosphatidylcholine group into the polymer chains. Time-resolved dynamic light scattering (DLS), combined with transmission electron microscopy (TEM), was employed to investigate the kinetics of morphology transition. Moreover, a dissipative particle dynamics (DPD) simulation method was applied to study the mechanism of sphere-to-rod transition. These experimental and simulation studies revealed that the hydrophilic phosphatidylcholine groups can create defects on the surfaces of spherical polyurethane micelles, thus, making positive contribution to adhesive collisions and leading to the fusion of spherical micelles into rod-like micelles. This finding provides new insight into the origins of rod-like polymer micelles, which is valuable for the design and preparation of novel polymeric drug carriers with tailored properties

Cell Internalizable and Intracellularly Degradable Cationic Polyurethane Micelles as a Potential Platform for Efficient Imaging and Drug Delivery

A cell internalizable and intracellularly degradable micellar system, assembled from multiblock polyurethanes bearing cell-penetrating gemini quaternary ammonium pendent groups in the side chain and redox-responsive disulfide linkages throughout the backbone, was developed for potential magnetic resonance imaging (MRI) and drug delivery. The nanocarrier is featured as a typical “cleavable core–internalizable shell–protective corona” architecture, which exhibits small size, positive surface charge, high loading capacity, and reduction-triggered destabilization. Furthermore, it can rapidly enter tumor cells and release its cargo in response to an intracellular level of glutathione, resulting in enhanced drug efficacy <i>in vitro</i>. The magnetic micelles loaded with superparamagnetic iron oxide (SPIO) nanoparticles demonstrate excellent MRI contrast enhancement, with <i>T</i>₂ relaxivity found to be affected by the morphology of SPIO-clustering inside the micelle core. The multifunctional carrier with good cytocompatibility and nontoxic degradation products can serve as a promising theranostic candidate for efficient intracellular delivery of anticancer drugs and real-time monitoring of therapeutic effect

Antibacterial and Biocompatible Cross-Linked Waterborne Polyurethanes Containing Gemini Quaternary Ammonium Salts

A cross-linked waterborne polyurethane (CPTMGPU) with long-term stability was developed from poly­(ethylene glycol) (PEG), polyoxytetramethylene glycol (PTMG), isophorone diisocyanate (IPDI), l-lysine, and its derivative diamine consisting of gemini quaternary ammonium salt (GQAS), using ethylene glycol diglycidyl ether (EGDE) as a cross-linker. Weight loss test, X-ray photoelectron spectroscopy (XPS) measurements, and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) were performed to prove the surface structure and stability of these CPTMGPU films. Furthermore, the GQAS-bearing CPTMGPUs show repeatable contact-active antibacterial efficacy against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria and do not show any inhibition effect against fibroblasts in vitro. After subcutaneous implantation in rats, the CPTMGPU films manifest good biocompatibility in vivo, despite the presence of a typical foreign body reaction toward surrounding tissues and mild systematic inflammation reaction that could be eliminated after a short implantation period, as demonstrated by histology and immunohistochemistry combined with interleukin (IL)-1β, IL-4, IL-6, IL-10, and TNF-α analysis though enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR). Therefore, these cross-linked waterborne polyurethanes hold great promise for antibacterial applications in vivo

Effects of Chain Rigidity on the Adsorption of a Polyelectrolyte Chain on Mixed Lipid Monolayer: A Monte Carlo Study

We apply Monte Carlo simulation to explore the adsorption of a positively charged polyelectrolyte on a lipid monolayer membrane, composed of electronically neutral, monovalent anionic and mulvitalent anionic phospholipids. We systematically assess the influence of various factors, including the intrinsic rigidity of the polyelectrolyte chain, the bead charge density of the polyelectrolyte, and the ionic strength of the saline solution, on the interfacial structural properties of the polyelectrolyte/monolayer complex. The enhancement of the polyelectrolyte chain intrinsic rigidity reduces the polyelectrolyte conformational entropy loss and the energy gains in electrostatic interaction, but elevates the segregated anionic lipid demixing entropy loss. This energy-entropy competition results in a nonmonotonic dependence of the polyelectrolyte/monolayer association strength on the degree of chain rigidity. The semiflexible polyelectrolyte, i.e., the one with an intermediate degree of chain rigidity, is shown to associate onto the ternary membane below a higher critical ionic concentration. In this ionic concentration regime, the semiflexible polyelectrolyte binds onto the monolayer more firmly than the pancake-like flexible one and exhibits a stretched conformation. When the chain is very rigid, the polyelectrolyte with bead charge density <i>Z</i>_b = +1 exhibits a larger tail and tends to dissociate from the membrane, whereas the one with <i>Z</i>_b= +2 can still bind onto the membrane in a bridge-like conformation. Our results imply that chain intrinsic rigidity serves as an efficient molecular factor for tailoring the adsorption/desorption transition and interfacial structure of the polyelectrolyte/monolayer complex

Toward the Next-Generation Nanomedicines: Design of Multifunctional Multiblock Polyurethanes for Effective Cancer Treatment

Specific accumulation of therapeutics at tumor sites to improve <i>in vivo</i> biodistribution and therapeutic efficacy of anticancer drugs is a major challenge for cancer therapy. Herein, we demonstrate a new generation of intelligent nanosystem integrating multiple functionalities in a single carrier based on multifunctional multiblock polyurethane (MMPU). The smart nanocarriers equipped with stealth, active targeting, and internalizable properties can ferry paclitaxel selectively into tumor tissue, rapidly enter cancer cells, and controllably release their payload in response to an intracellular acidic environment, thus resulting in an improved biodistribution and excellent antitumor activity <i>in vivo</i>. Our work provides a facile and versatile approach for the design and fabrication of smart intracellular targeted nanovehicles for effective cancer treatment, and opens a new era in the development of biodegradable polyurethanes for next-generation nanodelivery systems

Simultaneous Improvement of Oxidative and Hydrolytic Resistance of Polycarbonate Urethanes Based on Polydimethylsiloxane/Poly(hexamethylene carbonate) Mixed Macrodiols

The degradation behaviors including oxidation and hydrolysis of silicone modified polycarbonate urethanes were thoroughly investigated. These polyurethanes were based on polyhexamethylene carbonate (PHMC)/polydimethylsiloxane (PDMS) mixed macrodiols with molar ratio of PDMS ranging from 5% to 30%. It was proved that PDMS tended to migrate toward surface and even a small amount of PDMS could form a silicone-like surface. Macrophages-mediated oxidation process indicated that the PDMS surface layer was desirable to protect the fragile soft PHMC from the attack of degradative species. Hydrolysis process was probed in detail after immersing in boiling buffered water using combined analytical tools. Hydrolytically stable PDMS could act as protective shields for the bulk to hinder the chain scission of polycarbonate carbonyls whereas the hydrolysis of urethane linkages was less affected. Although the promoted phase separation at higher PDMS fractions lead to possible physical defects and mechanical compromise after degradation, simultaneously enhanced oxidation and hydrolysis resistance could be achieved for the polyurethanes with proper PDMS incorporation

Effects of Concentration and Ionization Degree of Anchoring Cationic Polymers on the Lateral Heterogeneity of Anionic Lipid Monolayers

We employed coarse-grained Monte Carlo simulations to investigate a system composed of cationic polymers and a phosphatidyl-choline membrane monolayer, doped with univalent anionic phosphatidylserine (PS) and tetravalent anionic phosphatidylinositol 4,5-bisphosphate (PIP₂) lipid molecules. For this system, we consider the conditions under which multiple cationic polymers can anchor onto the monolayer and explore how the concentration and ionization degree of the polymers affect the lateral rearrangement and fluidity of the negatively charged lipids. Our work shows that the anchoring cationic polymers predominantly bind the tetravalent anionic PIP₂ lipids and drag the PIP₂ clusters to migrate on the monolayer. The polymer/PIP₂ binding is found to be drastically enhanced by increasing the polymer ionization fraction, which causes the PIP₂ lipids to form into larger clusters and reduces the mobility of the polymer/PIP₂ complexes. As expected, stronger competition effects between anchoring polymers occur at higher polymer concentrations, for which each anchoring polymer partially dissociates from the monolayer and hence sequesters a smaller PIP₂ cluster. The desorbed segments of the anchored polymers exhibit a faster mobility on the membrane, whereas the PIP₂ clusters are closely restrained by the limited adhering cationic segments of anchoring polymers. We further demonstrate that the PIP₂ molecules display a hierarchical mobility in the PIP₂ clusters, which is regulated by the synergistic effect between the cationic segments of the polymers. The PS lipids sequester in the vicinity of the polymer/PIP₂ complexes if the tetravalent PIP₂ lipids cannot sufficiently neutralize the cationic polymers. Finally, we illustrate that the increase in the ionic concentration of the solution weakens the lateral clustering and the mobility heterogeneity of the charged lipids. Our work thus provides a better understanding of the fundamental biophysical mechanism of the concentration gradients and the hierarchical mobility of the anionic lipids in the membrane caused by the cationic polymer anchoring on length and time scales that are generally inaccessible by atomistic models. It also offers insight into the development and design of novel biological applications on the basis of the modulation of signaling lipids