Synthesis of a Series of Folate-Terminated Dendrimer-b-PNIPAM Diblock Copolymers: Soft Nanoelements That Self-Assemble into Thermo- and pH-Responsive Spherical Nanocompounds

Abstract

A series of well-defined bifunctional dendrimers bearing one azide and 5, 15, and 44 folate termini were synthesized via the divergent approach. Poly­(N-isopropylacrylamide) homopolymers PNIPAM-7k, PNIPAM-19k, and PNIPAM-64k were prepared using the reversible addition-fragmentation chain-transfer polymerization (60–67% yield) followed by end functionalization with a cyclooctyne derivative. A grafting-to approach through strain-promoted azide alkyne cycloaddition between the dendrimers and the PNIPAM afforded a series of dendrimer-b-PNIPAM diblock copolymers containing folates (G1-11k, G2-30k, and G3-95k). Investigation of the self-assembly process in aqueous media revealed the formation of thermo- and pH-responsive core–shell spherical micelles within the 70–160 nm size range with low polydispersities. Within the nanoperiodic concept, these dendrimer-b-PNIPAM copolymers behave as S1-type nanoelements that self-assemble into soft:soft spherical nanocompounds with a linear relationship between the molecular weight of the copolymers and the hydrodynamic diameter of the self-assembled nanospheres. The thermo- and pH-responsiveness of the micelles formed by the dendrimer-b-PNIPAM diblock copolymers bearing folates make them promising candidates for targeted drug delivery.

Engineering the Morphologies of Block Copolymer Particles from the Confined Self‐assembly within Emulsion Droplets†

“…In contrast, at a temperature higher than its LCST, PNIPAM chains become hydrophobic. [ 80‐83 ] Therefore, as…”

Stimuli-Responsive Dendritic Macromolecules for Optical Detection of Metal Ions and Acidic Vapors by the Photoinduced Electron Transfer Mechanism: Paper-Based Indicator for Food Spoilage Sensing

“…Dendritic macromolecules have lots of unique properties, which are well-defined nanostructures and unique morphologies, high concentration of functional groups at the surface, high solubility in aqueous media, high monodispersity, low viscosity, and modification ability with functional molecules. − These characteristics resulted in the development of dendritic nanostructures for a wide range of applications, including drug-delivery or gen-delivery systems, chemosensors, bioimaging, and tissue engineering. − Induction of stimuli-responsivity to dendrimers by their modification with intelligent molecules has been known as an attractive field of study. The pH- or temperature-responsive dendrimers are among the highly important smart nanocarriers in drug- or gen-delivery technology, − and the light-responsive dendrimers are highly applicable in bioimaging and photosensing applications. , Different types of dendrimers were modified with stimuli-responsive molecules using their surface functional groups, or in a classic approach, using a functional intelligent molecule as a core to growth of dendritic structures on the surface. − Therefore, the presence of acid, amine, or hydroxyl functional groups on dendrimers is inevitable for their reaction with functional molecules.…”