This review focuses on nanofabrication tools, based on soft lithography, which can generate a wide range of noble-metal structures with exceptional optical properties. These techniques offer a scalable and practical approach for producing arrays of complementary plasmonic structures (nanoholes and nanoparticles) and, in addition, expand the possible architectures of plasmonic materials because the metal building blocks can be organized over multiple length scales. We describe the preparation and characterization of five different systems: subwavelength nanohole arrays, finite arrays of nanoholes, microscale arrays of nanoholes, multiscale arrays of nanoparticles, and pyramidal particles. We also discuss how the surface plasmon resonances of these structures can be tuned across visible and near-infrared wavelengths by varying different parameters. Applications and future prospects of these nanostructured metals are addressed.

Nanotechnology can provide a critical advantage in developing strategies for cancer management and treatment by helping to improve the safety and efficacy of novel therapeutic delivery vehicles. This paper reports the fabrication of poly(lactic acid-co-glycolic acid)/siRNA nanoparticles coated with lipids for use as prostate cancer therapeutics made via a unique soft lithography particle molding process called PRINT (Particle Replication In Nonwetting Templates). The PRINT process enables high encapsulation efficiency of siRNA into neutral and monodisperse PLGA particles (32–46% encapsulation efficiency). Lipid-coated PLGA/siRNA PRINT particles were used to deliver therapeutic siRNA in vitro to knockdown genes relevant to prostate cancer.

The particle fabrication technique PRINT® was used to fabricate monodisperse size and shape specific poly(lactide-co-glycolide) particles loaded with the chemotherapeutic Docetaxel. The pharmacokinetics of two cylindrical shaped particles with diameter=80nm; height=320nm (PRINT-Doc-80×320) and d=200nm; h=200nm (PRINT-Doc-200×200) were compared to Docetaxel in mice bearing human ovarian carcinoma SKOV-3 flank xenografts. The Docetaxel plasma exposure was ~20-fold higher for both particles compared to docetaxel. Additionally, the volume of distribution (Vd) of Docetaxel in PRINT formulations was ~18-fold (PRINT-Doc-80×320) and ~33-fold (PRINT-Doc-200×200) lower than Docetaxel. The prolonged duration of Docetaxel in plasma when dosed with PRINT formulations subsequently lead to increased tumor exposure of Docetaxel from 0-168 hours (~53% higher for PRINT-Doc-80×320 and ~76% higher for PRINT-Doc-200×200 particles). PRINT-Doc-80×320 had lower exposures in the liver, spleen and lung compared with PRINT-Doc-200×200. Thus, the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system.

Nanomedicine has the potential to transform clinical care in the 21st century. However, a precise understanding of how nanomaterial design parameters such as size, shape and composition affect the mammalian immune system is a prerequisite for the realization of nanomedicine's translational promise. Herein, we make use of the recently developed Particle Replication in Non-wetting Template (PRINT) fabrication process to precisely fabricate particles across and the nano- and micro-scale with defined shapes and compositions to address the role of particle design parameters on the murine innate immune response in both in vitro and in vivo settings. We find that particles composed of either the biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) or the biocompatible polymer polyethylene glycol (PEG) do not cause release of pro-inflammatory cytokines nor inflammasome activation in bone marrow-derived macrophages. When instilled into the lungs of mice, particle composition and size can augment the number and type of innate immune cells recruited to the lungs without triggering inflammatory responses as assayed by cytokine release and histopathology. Smaller particles (80×320 nm) are more readily taken up in vivo by monocytes and macrophages than larger particles (6 µm diameter), yet particles of all tested sizes remained in the lungs for up to 7 days without clearance or triggering of host immunity. These results suggest rational design of nanoparticle physical parameters can be used for sustained and localized delivery of therapeutics to the lungs.

This paper investigates how structural features of noble metal nanoparticles affect their photothermal properties. Using PEEL, we fabricated a range of Au nanopyramid-like particles with surface plasmon resonances tunable from visible to near-infrared wavelengths. By systematically varying geometric parameters including size, shell thickness, and presence or absence of tips, we determined which factors were most important in heat generation. For solutions with the same Au content, we discovered that pyramidal particles with thin shells and having sharp tips showed the largest photothermal response.