Hybrid Silica-Coated PLGA Nanoparticles for Enhanced Enzyme-Based Therapeutics.

Some cancer cells rely heavily on non-essential biomolecules for survival, growth, and proliferation. Enzyme based therapeutics can eliminate these biomolecules, thus specifically targeting neoplastic cells; however, enzyme therapeutics are susceptible to immune clearance, exhibit short half-lives, and require frequent administration. Encapsulation of therapeutic cargo within biocompatible and biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) is a strategy for controlled release. Unfortunately, PLGA NPs exhibit burst release of cargo shortly after delivery or upon introduction to aqueous environments where they decompose via hydrolysis. Here, we show the generation of hybrid silica-coated PLGA (SiLGA) NPs as viable drug delivery vehicles exhibiting sub-200 nm diameters, a metastable Zeta potential, and high loading efficiency and content. Compared to uncoated PLGA NPs, SiLGA NPs offer greater retention of enzymatic activity and slow the burst release of cargo. Thus, SiLGA encapsulation of therapeutic enzymes, such as asparaginase, could reduce frequency of administration, increase half-life, and improve efficacy for patients with a range of diseases.

Acoustic Microcannons: Toward Advanced Microballistics.

Acoustically triggered microcannons, capable of loading and firing nanobullets (Nbs), are presented as powerful microballistic tools. Hollow conically shaped microcannon structures have been synthesized electrochemically and fully loaded with nanobullets made of silica or fluorescent microspheres, and perfluorocarbon emulsions, embedded in a gel matrix stabilizer. Application of a focused ultrasound pulse leads to the spontaneous vaporization of the perfluorocarbon emulsions within the microcannon and results in the rapid ejection of the nanobullets. Such Nbs "firing" at remarkably high speeds (on the magnitude of meters per second) has been modeled theoretically and demonstrated experimentally. Arrays of microcannons anchored in a template membrane were used to demonstrate the efficient Nbs loading and the high penetration capabilities of the ejected Nbs in a tissue phantom gel. This acoustic-microcannon approach could be translated into advanced microscale ballistic tools, capable of efficient loading and firing of multiple cargoes, and offer improved accessibility to target locations and enhanced tissue penetration properties.

Controlling the self-assembly of magnetic nanoparticles by competing dipolar and isotropic particle interactions.

Control over the self-assembly of magnetic nanoparticles (MNP) into superstructures due to different types of coupling is of interest in the development of "bottom-up" fabrication schemes. Here we realize a simple strategy for the systematic variation of particle interaction potential in magnetic nanoparticles. This is achieved by varying the effective surface potential by means of a co-surfactant introduced in the course of the synthesis process. As a consequence, the ability to form chain-like assemblies is affected by the resulting balance of attractive and repulsive forces. We use electron microscopy, electron diffraction, and light scattering methods to study a series of cobalt nanoparticles as a characteristic example of ferromagnetic MNP. We demonstrate experimentally and substantiate theoretically that the observed behavior results from a balance between magnetic dipole-dipole, steric, and electrostatic interactions.