A bolaamphiphilic cross-linked nanoassembly endowed with pH responsive degradation features has been designed and fabricated for stable noncovalent guest encapsulation and controlled release.

The self-assembly of a stimuli-responsive amphiphilic polymer has been of great interest in the area of targeted drug delivery applications. In this article, a new amphiphilic polyurethane with a hydrophobic backbone consisting of a redox-responsive self-immolative unit and hydrophilic pendant triethylene glycol, which is periodically grafted on the backbone by a tertiary amine group, has been designed and synthesized. This amphiphilic polymer self-assembles into a micellar nanostructure (investigated by dynamic light scattering and transmission electron microscopy) in an aqueous medium and shows guest encapsulation property. Furthermore, the pH-responsive nature leads to the formation of a positively charged nanoassembly at a tumor-relevant pH (∼6.5–6.8), which is probed by zeta potential measurements. As the backbone was constructed with self-immolative, redox-responsive functionality, degradation of the polymer was observed in the presence of a reducing agent, glutathione (GSH), which results in disassembly of the self-assembled structure followed by guest release as probed by UV–vis spectroscopy. The triggered degradation and pH-specific charge generation (from neutral to positive), we believe, will have implications in the design of biodegradable polymers as supramoleular scaffolds for biomedical applications.

Stabilizing noncovalently encapsulated guest molecules inside a nanoassembly constructed from amphiphilic polymers has become a very challenging effort in the area of targeted drug delivery of biomedical applications. The unwanted...

Stimuli-responsive amphiphilic polymer assemblies are of great interest in the area of targeted drug delivery applications as they can sequester guest molecules in one set of conditions and release them under another. Hence, developing a strategy of molar mass controlled synthesis, in-depth understanding of the thermodynamics of the self-assembly process, stabilization, and triggered guest release in a controlled fashion would be highly anticipated in the field of drug delivery applications. As polymer molar mass has a significant impact on the self-assembly process or material property of polymers, we focused on a methodology of controlled molar mass polyurethane synthesis using recycled plastic waste and synthesized a series of self-immolative amphiphilic polyurethanes of varying molar masses and polydispersity indexes. All of the polymers were equipped with periodically grafted triethyleneglycol monomethyl ether as a pendant, a redox-responsive disulfide bond, a tertiary amine, and an aromatic moiety on the backbone. In aqueous milieu, these polymers are found to form entropically driven nanoassemblies (ΔS > 0), which were further stabilized by supramolecular cross-linking via the synergistic effect of π−π stacking (aromatic moiety), H-bonding (urethane functionality), and hydrophobic interactions, which eventually amplifies the guest encapsulation stability. A guest release profile in the presence of a redox environment shows ∼65% release in a controlled fashion. Furthermore, the tertiary amine on the polymer backbone leads to the formation of positively charged nanoassemblies at the tumor-relevant pH (pH ∼ 6.5−6.8), which could potentially enhance the cellular uptake of nanocarriers in tumor cells. Thus, a strategy for molar mass controlled polyurethane synthesis, understanding the effect of polymer molar mass on thermodynamics of self-assembly, establishing a stable micellar nanostructure endowed with environment-specific surface charge modulation, and controlled guest release, we believe, will significantly contribute to the development of robust chemotherapeutics.

The role of solvents in the control over supramolecular interactions has been studied for decades in protein folding, soft material fabrication and long-range organization of functional organic π chromophores. Nonpolar...