PEGylated polymers for medicine: from conjugation to self-assembled systems.

Synthetic polymers have transformed society in many areas of science and technology, including recent breakthroughs in medicine. Synthetic polymers now offer unique and versatile platforms for drug delivery, as they can be "bio-tailored" for applications as implants, medical devices, and injectable polymer-drug conjugates. However, while several currently used therapeutic proteins and small molecule drugs have benefited from synthetic polymers, the full potential of polymer-based drug delivery platforms has not yet been realized.

Fluorogenic 1,3-dipolar cycloaddition within the hydrophobic core of a shell cross-linked nanoparticle.

Using either nitroxide mediated polymerization (NMP) or reversible addition fragmentation transfer (RAFT) techniques, novel block copolymers that present terminal acetylenes, in the side chain of the styrenic block, were obtained with narrow polydispersities and targeted molecular weights. For the conversion of these acetylene-functionalized polymers to amphiphilic block copolymers, RAFT techniques were preferred. Mild protection/deprotection chemistries were employed which were compatible with the incorporation of the acetylene functionality in the hydrophobic segment.

Shell click-crosslinked (SCC) nanoparticles: a new methodology for synthesis and orthogonal functionalization.

A new methodology for the preparation of well-defined core-shell nanoparticles was developed, based upon the employment of a multifunctional crosslinker to coincidently stabilize supramolecular polymer assemblies and imbed into the shell unique chemical functionalities. Amphiphilic diblock copolymers of poly(acrylic acid)(80)-b-poly(styrene)(90) that had been assembled into micelles and partially functionalized throughout the corona with alkynyl groups were utilized as Click-readied nanoscaffolds for the formation of shell Click-crosslinked nanoparticles (SCCs). Divergently grown dendrimers of the zero, first, second, and third generations having increasing numbers of azide terminating groups ((N(3))(2)-[G-0], (N(3))(4)-[G-1], (N(3))(8)-[G-2], and (N(3))(16)-[G-3], respectively) were investigated as crosslinkers via Click reactions with the alkynyl groups to form covalent linkages throughout the block copolymer micelle corona, thus forming a crosslinked shell.

Antigen-decorated shell cross-linked nanoparticles: synthesis, characterization, and antibody interactions.

Antigen-decorated shell cross-linked knedel-like nanoparticles (SCKs) were synthesized and studied as multivalent nanoscale surfaces from which antibody-binding units were presented in a manner that was designed to approach virus particle surfaces. The SCK nanostructures were fabricated with control over the number of antigenic groups, from mixed micellization of amphiphilic diblock copolymer building blocks that contained either an antigen (2,4-dinitrophenyl) or an ethylpropionate group at the hydrophilic alpha-chain terminus. Amphiphilic diblock copolymers were synthesized by atom transfer radical polymerization of tert-butyl acrylate and methyl acrylate sequentially from either a 2,4-dinitrophenyl-functionalized initiator or ethyl 2-bromopropionate, followed by selective removal of the tert-butyl groups to afford 2,4-dinitrophenyl-poly(acrylic acid)60-b-poly(methyl acrylate)60 (DNP-PAA(60)-b-PMA60) and poly(acrylic acid)70-b-poly(methyl acrylate) (PAA70-b-PMA70).

An assessment of the effects of shell cross-linked nanoparticle size, core composition, and surface PEGylation on in vivo biodistribution.

Amphiphilic core-shell nanoparticles have drawn considerable interest in biomedical applications. The precise control over their physicochemical parameters and the ability to attach various ligands within specific domains suggest shell cross-linked (SCK) nanoparticles may be used as multi-/polyvalent scaffolds for drug delivery. In this study, the biodistribution of four SCKs, differing in size, core composition, and surface PEGylation, was evaluated.

Synthesis, characterization, and bioavailability of mannosylated shell cross-linked nanoparticles.

Saccharide-functionalized shell cross-linked (SCK) polymer micelles designed as polyvalent nanoscaffolds for selective interactions with receptors on Gram negative bacteria were constructed from mixed micelles composed of poly(acrylic acid-b-methyl acrylate) and mannosylated poly(acrylic acid-b-methyl acrylate). The mannose unit was conjugated to the hydrophilic chain terminus of the amphiphilic diblock copolymer precursor, from which the SCK nanoparticles were derived, by the growth of the diblock copolymer from a mannoside functionalized atom transfer radical polymerization (ATRP) initiator. Mixed micelle formation between the amphiphilic diblock copolymer and mannosylated amphiphilic diblock copolymer was followed by condensation-based cross-linking between the acrylic acid residues present in the periphery of the polymer micelles to afford SCK nanoparticles.