Mathieu L. Viger

Low Power Upconverted Near‐IR Light for Efficient Polymeric Nanoparticle Degradation and Cargo Release

By encapsulating NaYF4 :Tm.Yb upconverting nanocrystals in UV-degradable polymer capsules, it is possible to access efficient polymer photodegradation and remotely controlled release using near-IR laser light at an unprecedentedly low power.

Collective activation of MRI agents via encapsulation and disease-triggered release

An activation mechanism based on encapsulated ultrasmall gadolinium oxide nanoparticles (Gd oxide NPs) in bioresponsive polymer capsules capable of triggered release in response to chemical markers of disease (i.e., acidic pH, H2O2) is presented. Inside the hydrophobic polymeric matrices, the Gd oxide NPs are shielded from the aqueous environment, silencing their ability to enhance water proton relaxation. Upon disassembly of the polymeric particles, activation of multiple contrast agents generates a strong positive contrast enhancement of >1 order of magnitude.

Near-infrared-induced heating of confined water in polymeric particles for efficient payload release.

Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution.

Label-Free Biosensing Based on Multilayer Fluorescent Nanocomposites and a Cationic Polymeric Transducer

This study describes the preparation and characterization of a DNA sensing architecture combining the molecular recognition capabilities of a cationic conjugated polymer transducer with highly fluorescent core-shell nanoparticles (NPs). The very structure of the probe-labeled NPs and the polymer-induced formation of NP aggregates maximize the proximity between the polymer donor and acceptor NPs that is required for optimal resonant energy transfer. Each hybridization event is signaled by a potentially large number of excited reporters following the efficient plasmon-enhanced energy transfer between target-activated polymer transducer and fluorophores located in the self-assembled core-shell aggregates, resulting in direct molecular detection of target nucleic acids at femtomolar concentrations.

Efficient red light photo-uncaging of active molecules in water upon assembly into nanoparticles

One-photon red visible light-responsive photocage–drug conjugate nanoparticles dissolve and release free drug upon irradiation.

Application of time-resolved fluorescence for direct and continuous probing of release from polymeric delivery vehicles

Though accurately evaluating the kinetics of release is critical for validating newly designed therapeutic carriers for in vivo applications, few methods yet exist for release measurement in real time and without the need for any sample preparation. Many of the current approaches (e.g. chromatographic methods, absorption spectroscopy, or NMR spectroscopy) rely on isolation of the released material from the loaded vehicles, which require additional sample purification and can lead to loss of accuracy when probing fast kinetics of release. In this study we describe the use of time-resolved fluorescence for in situ monitoring of small molecule release kinetics from biodegradable polymeric drug delivery systems. This method relies on the observation that fluorescent reporters being released from polymeric drug delivery systems possess distinct excited-state lifetime components, reflecting their different environments in the particle suspensions, i.e., confined in the polymer matrices or free in the aqueous environment. These distinct lifetimes enable real-time quantitative mapping of the relative concentrations of dye in each population to obtain precise and accurate temporal information on the release profile of particular carrier/payload combinations. We found that fluorescence lifetime better distinguishes subtle differences in release profiles (e.g. differences associated with dye loading) than conventional steady-state fluorescence measurements, which represent the averaged dye behavior over the entire scan. Given the methods applicability to both hydrophobic and hydrophilic cargo, it could be employed to model the release of any drug-carrier combination.

Metal-Enhanced Fluorescence and FRET in Multilayer Core-Shell Nanoparticles

In recent years, various methods for the synthesis of fluorescent core-shell nanostructures were developed, optimized, and studied thoroughly in our research group. Metallic cores exhibiting plasmonic properties in the UV and visible regions of the electromagnetic spectrum were used to increase substantially the brightness and stability of organic fluorophores encapsulated in silica shells. Furthermore, the efficiency and range of Forster resonant energy transfer (FRET) between donor and acceptor molecules located in the vicinity of the metallic core was shown to be enhanced. Such multilayer nanoparticle architectures offer, in addition to the aforementioned advantages, excellent chemical and physical stability, solubility in aqueous media, low toxicity, and high detectability. In view of these enviable characteristics, a plethora of applications have been envisioned in biology, analytical chemistry, and medical diagnostics. In this paper, advances in the development of multilayer core-shell luminescent nanoparticle structures and selected applications to bioanalytical chemistry will be described.