title: Strategies Toward Well-Defined Polymer Nanoparticles Inspired by Nature: Chemistry versus Versatility.
abstract: Polymeric nanoparticles are promising delivery platforms for various biomedical applications. One of the main challenges toward the development of therapeutic nanoparticles is the premature disassembly and release of the encapsulated drug. Among the different strategies to enhance the kinetic stability of polymeric nanoparticles, shell- and core-crosslinking have been shown to provide robust character, while creating a suitable environment for encapsulation of a wide range of therapeutics, including hydrophilic, hydrophobic, metallic, and small and large biomolecules, with gating of their release as well. The versatility of shell- and core-crosslinked nanoparticles is driven from the ease by which the structures of the shell- and core-forming polymers and crosslinkers can be modified. In addition, postmodification with cell-recognition moieties, grafting of antibiofouling polymers, or chemical degradation of the core to yield nanocages allow the use of these robust nanostructures as "smart" nanocarriers. The building principles of these multifunctional nanoparticles borrow analogy from the synthesis, supramolecular assembly, stabilization, and dynamic activity of the naturally driven biological nanoparticles such as proteins, lipoproteins, and viruses. In this review, the chemistry involved during the buildup from small molecules to polymers to covalently stabilized nanoscopic objects is detailed, with contrast of the strategies of the supramolecular assembly of polymer building blocks followed by intramicellar stabilization into shell-, core-, or core-shell-crosslinked knedel-like nanoparticles versus polymerization of polymers into nanoscopic molecular brushes followed by further intramolecular covalent stabilization events. The rational design of shell-crosslinked knedel-like nanoparticles is then elaborated for therapeutic packaging and delivery, with emphasis on the polymer chemistry aspects to accomplish the synthesis of such nanoparticulate systems.
authors.affiliation: Department of Chemistry, Texas A&M University, P.O. Box 30012, 3255 TAMU, College Station, Texas 77842-3012 ; Department of Chemistry, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, P.O. Box 30012, 3255 TAMU, College Station, Texas 77842-3012 ; Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Elsabahy
authors.affiliation: Department of Chemistry, Texas A&M University, P.O. Box 30012, 3255 TAMU, College Station, Texas 77842-3012 ; Department of Chemistry, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, P.O. Box 30012, 3255 TAMU, College Station, Texas 77842-3012 ; Department of Chemical Engineering, Texas A&M University, P.O. Box 30012, 3255 TAMU, College Station, Texas 77842-3012.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Wooley
keywords: biomimetic; biomimetic nanoparticles; block copolymers; nanocages; nanoparticles; polymer brushes; shell-crosslinked knedel-like nanoparticles