The effect of solvent quality on pathway-dependent solution-state self-assembly of an amphiphilic diblock copolymer

The cholesterol-functionalized polycarbonate-based diblock copolymer, PEG113-b-P(MTC-Chol)30, forms pathway-dependent nanostructures via dialysis-based solvent exchange. The initial organic solvent that dissolves or disperses the polymer dictates a self-assembly pathway. Depending upon the initial solvent, nanostructures of disk-like micelles, exhibiting asymmetric growth and hierarchical features, are accessible from a single amphiphilic precursor. Dioxane and tetrahydrofuran (THF) molecularly dissolve the block copolymer, but THF yields disks, while dioxane yields stacked disks after dialysis against water. Dimethylformamide and methanol display dispersed disks and then form stacked disk structures after dialysis. The path-dependent morphology was correlated to solubility parameters, an understanding of which offers routes to tailor self-assemblies with limited sets of building blocks.Agency for Science, Technology and Research (A*STAR)Published versio

Self-Assembly and Dynamics Driven by Oligocarbonate–Fluorene End-Functionalized Poly(ethylene glycol) ABA Triblock Copolymers

The closed assembly transition from polymers to micelles and open assembly to clusters are induced by supramolecular π–π stacking in model oligocarbonate–fluorene (F-TMC) end-group telechelic polymers. The critical micelle concentration (CMC) depends on the F-TMC degree of polymerization that further controls the weak micelle association and strong clustering of micelles regimes. Clustering follows a multistep equilibria model with average size scaling with concentration reduced by the CMC as <i>R</i> ∼ (<i>c</i>/CMC)^1/4. The F-TMC packing that drives the supramolecular self-assembly from polymers to micelles stabilizes these larger clusters. The clusters are characterized by internal relaxations by dynamic light scattering. This signifies that while F-TMC groups drive the clustering, the micelles interconnected via F-TMC bridging interactions remain coupled to the extent that the clusters relax via Rouse–Zimm dynamics, reminiscent of microgels

Fabrication and Characterization of Hybrid Stealth Liposomes

Next-generation liposome systems for anticancer and therapeutic delivery require the precise insertion of stabilizing polymers and targeting ligands. Many of these functional macromolecules may be lost to micellization as a competing self-assembly landscape. Here, hybrid stealth liposomes, which utilize novel cholesteryl-functionalized block copolymers as the molecular stabilizer, are explored as a scalable platform to address this limitation. The employed block copolymers offer resistance to micellization through multiple liposome insertion moieties per molecule. A combination of thermodynamic and structural investigations for a series of hybrid stealth liposome systems suggests that a critical number of cholesteryl moieties per molecule defines whether the copolymer will or will not insert into the liposome bilayer. Colloidal stability of formed hybrid stealth liposomes further corroborates the critical copolymer architecture value

Formation of Disk- and Stacked-Disk-like Self-Assembled Morphologies from Cholesterol-Functionalized Amphiphilic Polycarbonate Diblock Copolymers

A cholesterol-functionalized aliphatic cyclic carbonate monomer, 2-(5-methyl-2-oxo-1,3-dioxane-5-carboxyloyloxy)­ethyl carbamate (MTC-Chol), was synthesized. The organocatalytic ring-opening polymerization of MTC-Chol was accomplished by using <i>N</i>-(3,5-trifluoromethyl)­phenyl-<i>N</i>′-cyclohexylthiourea (TU) in combinations with bases such as 1,8-diazabicyclo[5.4.0]­undec-7-ene (DBU) and (−)-sparteine, and kinetics of polymerization was monitored. By using mPEG-OH as the macroinitiator, well-defined amphiphilic diblock copolymers mPEG₁₁₃-<i>b</i>-P­(MTC-Chol)_<i>n</i> (<i>n</i> = 4 and 11) were synthesized. Under aqueous conditions, these block copolymers self-assembled to form unique nanostructures. Disk-like micelles and stacked-disk morphology were observed for mPEG₁₁₃-<i>b</i>-P­(MTC-Chol)₄ and mPEG₁₁₃-<i>b</i>-P­(MTC-Chol)₁₁, respectively, by transmission electron microscopy (TEM). Small-angle neutron scattering supports the disk-like morphology and estimates the block copolymer micelle aggregation number in the dispersed solution. The hydrophobic nature of the cholesterol-containing block provides a versatile self-assembly handle to form complex nanostructures using biodegradable and biocompatible polymers for applications in drug delivery

Amphiphilic and Hydrophilic Block Copolymers from Aliphatic <i>N</i>‑Substituted 8‑Membered Cyclic Carbonates: A Versatile Macromolecular Platform for Biomedical Applications

Introduction of hydrophilic components, particularly amines and zwitterions, onto a degradable polymer platform, while maintaining precise control over the polymer composition, has been a challenge. Recognizing the importance of these hydrophilic residues in multiple aspects of the nanobiomedicine field, herein, a straightforward synthetic route to access well-defined amphiphilic and hydrophilic degradable block copolymers from diethanolamine-derived functional eight-membered <i>N</i>-substituted aliphatic cyclic carbonates is reported. By this route, tertiary amine, secondary amine, and zwitterion residues can be incorporated across the polymer backbone. Demonstration of pH-responsiveness of these hydrophilic residues and their utility in the development of drug-delivery vehicles, catered for the specific requirements of respective model drugs (doxorubicin and diclofenac sodium salt) are shown. As hydrophilic components in degradable polymers play crucial roles in the biological interactions, these materials offers opportunities to expand the scope and applicability of aliphatic cyclic carbonates. Our approach to these functional polycarbonates will expand the range of biocompatible and biodegradable synthetic materials available for nanobiomedicine, including drug and gene delivery, antimicrobials, and hydrophilic polymers as poly­(ethylene glycol) (PEG) alternatives

Biodegradable Strain-Promoted Click Hydrogels for Encapsulation of Drug-Loaded Nanoparticles and Sustained Release of Therapeutics

Biodegradable polycarbonate-based ABA triblock copolymers were synthesized via organocatalyzed ring-opening polymerization and successfully formulated into chemically cross-linked hydrogels by strain-promoted alkyne–azide cycloaddition (SPAAC). The synthesis and cross-linking of these polymers are copper-free, thereby eliminating the concern over metallic contaminants for biomedical applications. Gelation occurs rapidly within a span of 60 s by simple mixing of the azide- and cyclooctyne-functionalized polymer solutions. The resultant hydrogels exhibited pronounced shear-thinning behavior and could be easily dispensed through a 22G hypodermic needle. To demonstrate the usefulness of these gels as a drug delivery matrix, doxorubicin (DOX)-loaded micelles prepared using catechol-functionalized polycarbonate copolymers were incorporated into the polymer solutions to eventually form micelle/hydrogel composites. Notably, the drug release rate from the hydrogels was significantly more gradual compared to the solution formulation. DOX release from the micelle/hydrogel composites could be sustained for 1 week, while the release from the micelle solution was completed rapidly within 6 h of incubation. Cellular uptake of the released DOX from the micelle/hydrogel composites was observed at 3 h of incubation of human breast cancer MDA-MB-231 cells. A blank hydrogel containing PEG-(Cat)₁₂ micelles showed almost negligible toxicity on MDA-MB-231cells where cell viability remained high at >80% after treatment. When the cells were treated with the DOX-loaded micelle/hydrogel composites, there was a drastic reduction in cell viability with only 25% of cells surviving the treatment. In all, this study introduces a simple method of formulating hydrogel materials with incorporated micelles for drug delivery applications

Polymersomes as Stable Nanocarriers for a Highly Immunogenic and Durable SARS-CoV-2 Spike Protein Subunit Vaccine

10.1021/acsnano.1c01243ACS NANO151015754-1577