Programmable Release of Multiple Protein Drugs from Aptamer-Functionalized Hydrogels via Nucleic Acid Hybridization

Mark R. Battig , Boonchoy Soontornworajit , andYong Wang *

Department of Chemical, Materials, and Biomolecular Engineering, University of Connecticut, Storrs, Connecticut 06269, United States

J. Am. Chem. Soc., 2012, 134 (30), pp 12410–12413

DOI: 10.1021/ja305238a

Publication Date (Web): July 23, 2012

Copyright © 2012 American Chemical Society

Polymeric delivery systems have been extensively studied to achieve localized and controlled release of protein drugs. However, it is still challenging to control the release of multiple protein drugs in distinct stages according to the progress of disease or treatment. This study successfully demonstrates that multiple protein drugs can be released from aptamer-functionalized hydrogels with adjustable release rates at predetermined time points using complementary sequences (CSs) as biomolecular triggers. Because both aptamer–protein interactions and aptamer–CS hybridization are sequence-specific, aptamer-functionalized hydrogels constitute a promising polymeric delivery system for the programmable release of multiple protein drugs to treat complex human diseases.

Photodegradable Macromers and Hydrogels for Live Cell Encapsulation and Release

Donald R. Griffin and Andrea M. Kasko *

Department of Bioengineering, University of California, Los Angeles, 410 Westwood Plaza, 5121 Eng V, Los Angeles, California 90095, United States

J. Am. Chem. Soc., 2012, 134 (31), pp 13103–13107

DOI: 10.1021/ja305280w

Publication Date (Web): July 5, 2012

Copyright © 2012 American Chemical Society

Hydrogel scaffolds are commonly used as 3D carriers for cells because their properties can be tailored to match natural extracellular matrix. Hydrogels may be used in tissue engineering and regenerative medicine to deliver therapeutic cells to injured or diseased tissue through controlled degradation. Hydrolysis and enzymolysis are the two most common mechanisms employed for hydrogel degradation, but neither allows sequential or staged release of cells. In contrast, photodegradation allows external real-time spatial and temporal control over hydrogel degradation, and allows for staged and sequential release of cells. We synthesized and characterized a series of macromers incorporating photodegradbale ortho-nitrobenzyl (o-NB) groups in the macromer backbone. We formed hydrogels from these macromers via redox polymerization and quantified the apparent rate constants of degradation (k_app) of each via photorheology at 370 nm, 10 mW/cm². Decreasing the number of aryl ethers on the o-NB group increases k_app, and changing the functionality from primary to seconday at the benzylic site dramatically increases k_app. Human mesenchymal stem cells (hMSCs) survive encapsulation in the hydrogels (90% viability postencapsulation). By exploiting the differences in reactivity of two different o-NB linkers, we quantitatively demonstrate the biased release of one stem cell population (green-fluoroescent protein expressing hMSCs) over another (red-fluorescent protein expressing hMSCs).

CdS–Polymer Nanocomposites and Light-Emitting Fibers by In Situ Electron-Beam Synthesis and Lithography

1. Luana Persano^1,2,*, 
2. Andrea Camposeo^1,2,
3. Francesca Di Benedetto¹, 
4. Ripalta Stabile¹,
5. Anna M. Laera⁴, 
6. Emanuela Piscopiello⁴,
7. Leander Tapfer⁴, 
8. Dario Pisignano^1,2,3

Article first published online: 26 JUL 2012

DOI: 10.1002/adma.201202440

A straightforward, electron-beam induced synthesis and patterning approach to the in situ generation of CdS nanocrystals in nanocomposite films and light-emitting electrospun nanofibers is used. Smartly combining room-temperature nanoimprinting, electrospinning, and electron-beam decomposition of nanocrystal precursors and subsequent nucleation of nanoparticles in a polymer matrix allows exploitation of the most favorable flow conditions of organics to produce various nanocomposite nanostructures.

Controlled Assembly and Plasmonic Properties of Asymmetric Core–Satellite Nanoassemblies

Jun Hee Yoon, Jonghui Lim, and Sangwoon Yoon*

Department of Chemistry, Institute of Nanosensor and Biotechnology, Dankook University, 152 Jukjeon-ro, Suji-gu, Yongin, Gyeonggi 448-701, Korea

ACS Nano, Article ASAP

DOI: 10.1021/nn302264f

Publication Date (Web): July 24, 2012

Copyright © 2012 American Chemical Society

The assembly of noble metal nanoparticles offers an appealing means to control and enhance the plasmonic properties of nanostructures. However, making nanoassemblies with easily modifiable gap distances with high efficiency has been challenging. Here, we report a novel strategy to assemble gold nanoparticles (AuNPs) into Janus-type asymmetric core–satellite nanostructures. Markedly different desorption efficiency between large and small AuNPs in ethanol allows us to prepare the asymmetric core–satellite nanoassemblies in a dispersed colloidal state with near 100% purity. The resulting nanoassemblies have well-defined structures in which a core AuNP (51 nm) is covered by an average of 13 ± 3 satellite AuNPs (13 nm) with part of the core surfaces left unoccupied. Strong surface plasmon coupling is observed from these nanoassemblies as a result of the close proximity between the core and the satellites, which appears significantly red-shifted from the surface plasmon resonance frequencies of the constituting nanoparticles. The dependence of the surface plasmon coupling on a gap distance of less than 3 nm is systematically investigated by varying the length of the alkanedithiol linkers. The asymmetric core–satellite nanoassemblies also serve as an excellent surface-enhanced Raman scattering substrate with an enhancement factor of 10⁶. Finally, we demonstrate that the presented assembly method is extendible to the preparation of compositionally heterogeneous core–satellite nanoassemblies.

Polystyrene Particles Reveal Pore Substructure As They Translocate

Matthew Pevarnik†, Ken Healy†‡*, Maria EugeniaToimil-Molares§, Alan Morrison‡, Sonia E. Létant, and Zuzanna S. Siwy†*

^† Department of Physics and Astronomy, University of California, Irvine, Irvine, California 92697, United States

^‡ Department of Electrical and Electronic Engineering,University College Cork, Cork, Ireland

^§ Department of Materials Science, GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany

 Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550, United States

In this article, we report resistive-pulse sensing experiments with cylindrical track-etched PET pores, which reveal that the diameters of these pores fluctuate along their length. The resistive pulses generated by polymer spheres passing through these pores have a repeatable pattern of large variations corresponding to these diameter changes. We show that this pattern of variations enables the unambiguous resolution of multiple particles simultaneously in the pore, that it can detect transient sticking of particles within the pore, and that it can confirm whether any individual particle completely translocates the pore. We demonstrate that nonionic surfactant has a significant impact on particle velocity, with the velocity decreasing by an order of magnitude for a similar increase in surfactant concentration. We also show that these pores can differentiate by particle size and charge, and we explore the influence of electrophoresis, electroosmosis, and pore size on particle motion. These results have practical importance for increasing the speed of resistive-pulse sensing, optimizing the detection of specific analytes, and identifying particle shapes.

Direct Visualization of the Movement of a Single T7 RNA Polymerase and Transcription on a DNA Nanostructure†

1. Dr. Masayuki Endo^1,3,*, 
2. Koichi Tatsumi²,
3. Kosuke Terushima², 
4. Yousuke Katsuda²,
5. Kumi Hidaka², 
6. Prof. Yoshie Harada¹, 
7. Prof. Hiroshi Sugiyama^1,2,3,*

Article first published online: 29 JUL 2012

DOI: 10.1002/anie.201201890

Snapshots of transcription: Movement of a single molecule of T7 RNA polymerase (RNAP) along a double-stranded DNA (dsDNA) template attached to a DNA origami platform (green, see scheme) was recorded using high-speed AFM. A one kilobase template dsDNA containing the T7 promoter was used to record AFM images of transcription of the template dsDNA by RNAP and the resulting biotinylated RNA product was detected by streptavidin-labeling.

Ordered Arrays of Native Chromatin Molecules for High-Resolution Imaging and Analysis

Aline Cerf, Harvey C. Tian, and Harold G. Craighead*

School of Applied and Engineering Physics, Cornell University, Ithaca, New York 14853, United States

ACS Nano, Article ASAP

DOI: 10.1021/nn3023624

Publication Date (Web): July 21, 2012

Copyright © 2012 American Chemical Society

Individual chromatin molecules contain valuable genetic and epigenetic information. To date, there have not been reliable techniques available for the controlled stretching and manipulation of individual chromatin fragments for high-resolution imaging and analysis of these molecules. We report the controlled stretching of single chromatin fragments extracted from two different cancerous cell types (M091 and HeLa) characterized through fluorescence microscopy and atomic force microscopy (AFM). Our method combines soft lithography with molecular stretching to form ordered arrays of more than 250 000 individual chromatin fragments immobilized into a beads-on-a-string structure on a solid transparent support. Using fluorescence microscopy and AFM, we verified the presence of histone proteins after the stretching and transfer process.