Kurt Breitenkamp

Polymeric micelles for drug delivery

Polymeric micelles have been the subject of many studies in the field of drug delivery for the past two decades. The interest has specifically been focused on the potential application of polymeric micelles in three major areas in drug delivery: drug solubilisation, controlled drug release and drug targeting. In this context, polymeric micelles consisting of poly(ethylene oxide)-b-poly(propylene oxide), poly(ethylene oxide)-b-poly(ester)s and poly(ethylene oxide)-b-poly(amino acid)s have shown a great promise and are in the front line of development for various applications. The purpose of this manuscript is to provide an update on the current status of polymeric micelles for each application and highlight important parameters that may lead to the development of successful polymeric micellar systems for individual delivery requirements.

Functional virus-based polymer-protein nanoparticles by atom transfer radical polymerization.

Viruses and virus-like particles (VLPs) are useful tools in biomedical research. Their defined structural attributes make them attractive platforms for engineered interactions over large molecular surface areas. In this report, we describe the use of VLPs as multivalent macroinitiators for atom transfer radical polymerization. The introduction of chemically reactive monomers during polymerization provides a robust platform for post-synthetic modification via the copper-catalyzed azide-alkyne cycloaddition reaction. These results provide the basis to construct nanoparticle delivery vehicles and imaging agents using protein-polymer conjugates.

Synergistic action of fibroblast growth factor-2 and transforming growth factor-beta1 enhances bioprinted human neocartilage formation

Bioprinting as a promising but unexplored approach for cartilage tissue engineering has the advantages of high throughput, digital control, and highly accurate placement of cells and biomaterial scaffold to the targeted 3D locations with simultaneous polymerization. This study tested feasibility of using bioprinting for cartilage engineering and examined the influence of cell density, growth, and differentiation factors. Human articular chondrocytes were printed at various densities, stimulated transiently with growth factors and subsequently with chondrogenic factors. Samples were cultured for up to 4 weeks to evaluate cell proliferation and viability, mechanical properties, mass swelling ratio, water content, gene expression, ECM production, DNA content, and histology. Bioprinted samples treated with FGF‐2/TGF‐β1 had the best chondrogenic properties among all groups apparently due to synergistic stimulation of cell proliferation and chondrogenic phenotype. ECM production per chondrocyte in low cell density was much higher than that in high cell seeding density. This finding was also verified by mechanical testing and histology. In conclusion, cell seeding density that is feasible for bioprinting also appears optimal for human neocartilage formation when combined with appropriate growth and differentiation factors. Biotechnol. Bioeng. 2012;109: 2357–2368.

Relative Performance of Alkynes in Copper-Catalyzed Azide-Alkyne Cycloaddition

Copper-catalyzed azide-alkyne cycloaddition (CuAAC) has found numerous applications in a variety of fields. We report here only modest differences in the reactivity of various classes of terminal alkynes under typical bioconjugative and preparative organic conditions. Propargyl compounds represent an excellent combination of azide reactivity, ease of installation, and cost. Electronically activated propiolamides are slightly more reactive, at the expense of increased propensity for Michael addition. Certain alkynes, including tertiary propargyl carbamates, are not suitable for bioconjugation due to copper-induced fragmentation. A fluorogenic probe based on such reactivity is available in one step from rhodamine 110 and can be useful for optimization of CuAAC conditions.

Encapsidated Atom-Transfer Radical Polymerization in Qβ Virus-like Nanoparticles

Virus-like particles (VLPs) are unique macromolecular structures that hold great promise in biomedical and biomaterial applications. The interior of the 30 nm-diameter Qβ VLP was functionalized by a three-step process: (1) hydrolytic removal of endogenously packaged RNA, (2) covalent attachment of initiator molecules to unnatural amino acid residues located on the interior capsid surface, and (3) atom-transfer radical polymerization of tertiary amine-bearing methacrylate monomers. The resulting polymer-containing particles were moderately expanded in size; however, biotin-derivatized polymer strands were only very weakly accessible to avidin, suggesting that most of the polymer was confined within the protein shell. The polymer-containing particles were also found to exhibit physical and chemical properties characteristic of positively charged nanostructures, including the ability to easily enter mammalian cells and deliver functional small interfering RNA.

Photodynamic activity of viral nanoparticles conjugated with C60

The development of viral nanoparticles (VNP) displaying multiple copies of the buckyball (C(60)) and their photodynamic activity is described. VNP-C(60) conjugates were assembled using click chemistry. Cell uptake and cell killing using white light therapy and a prostate cancer cell line is demonstrated.