Versatile surface micropatterning and functionalization enabled by microcontact printing of poly(4-aminostyrene).

Microcontact printing (µCP) of polyelectrolytes is a facile and powerful method for surface micro/nanopatterning and functionalization. Poly(4-aminostyrene) (PAS) is a polyelectrolyte that can be converted to aryldiazonium salt and exhibits pH-dependent hydrophobicity. Here we demonstrate µCP of PAS and the expansion of this technique in various directions. First, the microcontact-printed PAS can be diazotized to micropattern biomolecules including DNA and protein and nanomaterials including single-walled carbon nanotubes and gold nanoparticles. Second, the diazotized PAS enables µCP of a metallic structure on a carbon surface. Third, the hydrophobic nature of PAS at the neutral pH allows the microcontact-printed PAS-based polyelectrolyte multilayer to be used as masks for wet etching. Lastly, this technique allows facile fabrication of highly engineered microparticles with a unique structure. Overall, this work has established a novel µCP platform with various potential applications.

Nanocellulose templated growth of ultra-small bismuth nanoparticles for enhanced radiation therapy.

An unmet need in nanomedicine is to prepare biocompatible and renal clearable nanoparticles by controlling the diameter, composition and surface properties of the nanoparticles. This paper reports cellulose nanofiber templated synthesis of ultra-small bismuth nanoparticles, and their uses in enhanced X-ray radiation therapy. The interstitial spaces between adjacent fibers are the adsorption sites of bismuth ions and also stabilize nanoparticles generated by chemical reduction. The sizes of nanoparticles are tailored in the 2-10 nm range using cellulose nanofibers with various amounts of carboxyl groups. In vitro cytotoxicity, reactive oxygen species (ROS) and in vivo animal tests with tumor-bearing mice are studied in order to enhance X-ray radiation therapy using cellulose nanofiber-templated bismuth nanoparticles. Bismuth nanoparticles show strong X-ray attenuation ability, concentration-dependent cytotoxicity and high level production of ROS upon X-ray exposure, which is consistent with enhanced cellular damage and retarded growth of tumors in animals.

Enhanced radiation therapy with multilayer microdisks containing radiosensitizing gold nanoparticles.

A challenge of X-ray radiation therapy is that high dose X-rays at therapeutic conditions damage normal cells. This paper describes the use of gold nanoparticle-loaded multilayer microdisks to enhance X-ray radiation therapy, where each microdisk contains over 10(5) radiosensitizing nanoparticles. The microdisks are attached on cell membranes through electrostatic interaction. Upon X-ray irradiation, more photoelectrons and Auger electrons are generated in the vicinity of the nanoparticles, which cause water ionization and lead to the formation of free radicals that damage the DNA of adjacent cancer cells. By attaching a large amount of gold nanoparticles on cancer cells, the total X-ray dose required for DNA damage and cell killing can be reduced. Due to their controllable structure and composition, multilayer microdisks can be a viable choice for enhanced radiation therapy with nanoparticles.

Facile functionalization and assembly of live cells with microcontact-printed polymeric biomaterials.

The functionalization and assembly of live cells with microfabricated polymeric biomaterials have attracted considerable interest in recent years, but the conventional methods suffer from high cost, high complexity, long processing time or inadequate capability. The present study reports on the development of a novel method for functionalizing and assembling live cells by integrating microcontact printing of polymeric biomaterials with a temperature-sensitive sacrificial layer prepared by spin-coating. This method has been used not only to functionalize live cells with microscopic polyelectrolyte and thermoplastic structures of various sizes and shapes, but also to assemble the cells into macroscopic stripes and sheets. The method is applicable to multiple types of cells, including human leukemic cells, mouse embryonic stem cells and human mesenchymal stem cells in the forms of single cells and cell aggregates. In addition, the microcontact-printed structures can be prepared using biodegradable and biocompatible polyelectrolytes and thermoplastic. The unique combination of low cost, ease of use and high versatility renders this method potentially useful for diverse biomedical applications, including drug delivery, cell tracking and tissue engineering.

Asymmetric biodegradable microdevices for cell-borne drug delivery.

Use of live cells as carriers for drug-laden particulate structures possesses unique advantages for drug delivery. In this work, we report on the development of a novel type of particulate structures called microdevices for cell-borne drug delivery. The microdevices were fabricated by soft lithography with a disklike shape. Each microdevice was composed of a layer of biodegradable thermoplastic such as poly(lactic-co-glycolic acid). One face of the thermoplastic layer was covalently grafted with a cell-adhesive polyelectrolyte such as poly-l-lysine. This asymmetric structure allowed the microdevices to bind to live cells through bulk mixing without causing cell aggregation. Moreover, the cell-microdevice complexes were largely stable, and the viability and proliferation ability of the cells were not affected by the microdevices over a week. In addition, sustained release of a mock drug from the microdevices was demonstrated. This type of microdevice promises to be clinically useful for sustained intravascular drug delivery.

Gold nanoparticle-packed microdisks for multiplex Raman labelling of cells.

Micro/nanoparticles containing densely packed gold nanoparticles (AuNPs) possess unique properties potentially useful for various biomedical applications. The micro/nanoparticles are conventionally produced by the bottom-up methods, which have limited capability for controlling the particle size, shape and structure. This article reports development of a top-down method that integrates layer-by-layer assembly and microcontact printing to fabricate disk-shaped microparticles named microdisks composed of densely packed AuNPs. This method allows precise control of not only the size, shape and structure of the microdisks but also the amount of the AuNPs in the microdisks. The microdisks can be loaded with different Raman reporters to generate characteristic surface-enhanced Raman scattering spectra under the near infrared excitation over a centimetre-scale lens-sample distance. Moreover, the microdisks can be attached to single live cells. This microdisk platform holds potential for multiplex Raman labelling of therapeutic cells for in vivo tracking of the cells.