Block copolymer nanoparticles of controlled sizes via ring‐opening metathesis polymerization

Abstract

This article describes the formation and characterization of self‐assembled nanoparticles of controlled sizes based on amphiphilic block copolymers synthesized by ring‐opening metathesis polymerization. We synthesized a novel hydrophobic derivative of norbornene; this monomer could be polymerized using Grubbs' catalyst [Cl2Ru(CHPh)(PCy3)2] forming polymers of controlled molecular weight. We synthesized amphiphilic block copolymers of controlled composition and showed that they assemble into nanoparticles of controlled size. The nanoparticles were characterized using dynamic light scattering and transmission electron microscopy. Tuning the composition of the block copolymer enables the tuning of the diameters of the nanoparticles in the 30‐ to 80‐nm range. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3352–3359, 2004

Synthesis of homopolymers and copolymers containing an active ester of acrylic acid by RAFT: Scaffolds for controlling polyvalent ligand display

“…We and others have also used this concept to synthesize polyvalent inhibitors for pathogens and toxins that are orders of magnitude more potent than the corresponding monovalent inhibitors 5–16. These polyvalent inhibitors consist of multiple copies of a suitable ligand (e.g., a peptide or a sugar) attached to a scaffold 1–19. Linear polymers are attractive scaffolds for the polyvalent display of ligands1,2,12,13,20–22, and polymeric polyvalent inhibitors are often synthesized by the reaction of ligands with activated polymers – homopolymers or copolymers containing reactive monomers.…”

Phosphonic acid‐based amphiphilic diblock copolymers derived from ROMP

“…3 Ring-opening metathesis polymerization (ROMP) is a versatile technique for the preparation of well-defined block copolymers with narrow distribution of molecular weights. Several amphiphilic block copolymers obtained by the ROMP pathway have been investigated in the literature and were shown to form micelles and nanoparticles, [4][5][6][7][8][9][10][11][12][13][14] and used as drug delivery materials. [15][16][17] Phosphorus-containing polymers have broad application areas; besides their flameretardant properties, 18 they are also used in biomaterials for their adhesive properties to metals, bone, and dentin.…”

Design of Polyvalent Polymer Therapeutics

“…The advantages of using hub-and-spoke scaffolds, such as the βCD-based anthrax toxin inhibitor previously described, have also been recognized; matching the valency of the therapeutic to that of the target is more economical, and the resulting potency can be greater on a per-ligand basis [77]. Other polymeric scaffolds such as dendrimers [23], polymeric micelles [49,50], and polymersomes [80] are also amenable to polyvalent functionalization and may expand the therapeutic potential of polyvalent polymer scaffolds, as they have the added benefit of being able to transport cargo. It should be noted that the therapeutic potential of polyvalent systems is not limited to preventing undesired biological interactions (such as in inhibition of viral infection and bacterial toxin assembly) but can also include increasing the potency of signaling proteins such as Sonic hedgehog [81].…”

“…Micelles created from amphiphilic block copolymers often exhibit greater stability and have lower critical micellar concentrations relative to analogous micelles formed from low-molecular-weight surfactants, making them good candidates for therapeutics (Scheme 11.1). [49] demonstrated the preparation of self-assembling polymer micelles of controlled size by ring-opening metathesis polymerization (ROMP) to synthesize an amphiphilic block copolymer. The living polymerization technique, depicted in Scheme 11.2, first allowed for the synthesis of a hydrophobic homopolymer with good control over the degree of polymerization (DP) by varying the ratio of monomer to initiator (Figure 11.1).…”

“…The second stage of polymerization, in tetrahydrofuran (THF), added a hydrophilic block to the end of the hydrophobic block. The block copolymers then self-assembled in an aqueous solvent such that the hydrophobic block was contained within the hydrophilic exterior, and the hydrodynamic radii of the resulting micelles were dependent on the DP of the various block copolymer samples [49]. Being on the exterior, the hydrophilic block could also be potentially conjugated with a polyvalent display of ligands via the repeating carboxyl functionality.…”