Tennyson L. Doane

The unique role of nanoparticles in nanomedicine: imaging, drug delivery and therapy.

This critical review will present the role of nanoparticles (NPs) in the directions that are vital to the new field of nanomedicine, including imaging and drug delivery. We reflect on the physical properties that make NPs advantageous for in vivo efficacy, and review recent advances in major NP based biomedical applications. Critical questions of transport, uptake, and clearance will be discussed and illustrated through the success and opportunities of NP imaging and therapy on a photodynamic therapy (PDT) based NP system that has been developed in our lab over the past decade (540 references).

Nanoparticle mediated non-covalent drug delivery

The use of nanoparticles (NPs) for enhanced drug delivery has been heavily explored during the last decade. Within the field, it is has become increasingly apparent that the physical properties of the particles themselves dictate their efficacy, and the relevant non-covalent chemistry at the NP interface also influences how drugs are immobilized and delivered. In this review, we reflect on the physical chemistry of NP mediated drug delivery (and more specifically, non-covalent drug delivery) at the three main experimental stages of drug loading, NP-drug conjugate transport, and the resulting cellular drug delivery. Through a critical evaluation of advances in drug delivery within the last decade, an outlook for biomedical applications of nanoscale transport vectors will be presented.

Addressing Brain Tumors with Targeted Gold Nanoparticles: A New Gold Standard for Hydrophobic Drug Delivery?

EGF-modified Au NP-Pc 4 conjugates showed 10-fold improved selectivity to the brain tumor compared to untargeted conjugates. The hydrophobic photodynamic therapy drug Pc 4 can be delivered efficiently into glioma brain tumors by EGF peptide-targeted Au NPs. Compared to the untargeted conjugates, EGF-Au NP-Pc 4 conjugates showed 10-fold improved selectivity to the brain tumor. This delivery system holds promise for future delivery of a wider range of hydrophobic therapeutic drugs for the treatment of hard-to-reach cancers.

Measuring Electron and Hole Transfer in Core/Shell Nanoheterostructures

Using femtosecond transient absorption and time-resolved photoluminescence spectroscopy, we studied the electron versus hole dynamics in photoexcited quasi-type-II heterostructured nanocrystals with fixed CdTe core radii and varying CdSe shell coverage. By choosing the pump wavelength in resonance with the core or the shell states, respectively, we were able to measure the excited electron and hole dynamics selectively. Both, the core- and the shell-excited CdTe/CdSe nanocrystals showed the same spectral emission and photoluminescence lifetimes, indicating that ultrafast electron and hole transfer across the core/shell interface resulted in the identical long-lived charge transfer state. Both charge carriers have subpicosecond transfer rates through the interface, but the subsequent relaxation rates of the hole (τ(dec) ∼ 800 ps) and electron (τ(avg) ∼ 8 ps) are extremely different. On the basis of the presented transient absorption measurements and fitting of the steady-state spectra, we find that the electron transfer occurs in the Marcus inverted region and mixing between the CdTe exciton and charge transfer states takes place and therefore needs to be considered in the analysis.

Near Infrared Light-Triggered Drug Generation and Release from Gold Nanoparticle Carriers for Photodynamic Therapy

A photoprecursor Pc 227 is covalently bound onto gold nanoparticles (Au NPs) to produce the known photodynamic therapy (PDT) drug Pc 4 upon 660 nm photoirradiation. The photochemical formation of the photoproduct Pc 4 is identified by spectroscopy, chromatography, and mass spectrometry and its PDT efficacy is equal to Pc 4 when administered non-covalently by Au NPs, with the added benefit of improved covalent delivery and targeted NIR-triggered release from the covalent Pc 227-Au NP conjugate, while during transport the attached Pc 227 is quenched by the Au NP and PDT inactivated.

Nanoparticles for imaging and treating brain cancer

Brain cancer tumors cause disruption of the selective properties of vascular endothelia, even causing disruptions in the very selective blood-brain barrier, which are collectively referred to as the blood-brain-tumor barrier. Nanoparticles (NPs) have previously shown great promise in taking advantage of this increased vascular permeability in other cancers, which results in increased accumulation in these cancers over time due to the accompanying loss of an effective lymph system. NPs have therefore attracted increased attention for treating brain cancer. While this research is just beginning, there have been many successes demonstrated thus far in both the laboratory and clinical setting. This review serves to present the reader with an overview of NPs for treating brain cancer and to provide an outlook on what may come in the future. For NPs, just like the blood-brain-tumor barrier, the future is wide open.

Electrophoretic mobilities of PEGylated gold NPs

Electromigration of nanoparticles (NPs) is relevant to many technological and biological applications. We correlate the experimentally observed electromigration of Au NPs with a closed-form theoretical model that furnishes key NP characteristics, including the previously unknown values of Au NP core ζ-potential, PEG-corona permeability, and particle-hydrogel friction coefficient. More generally, the theory furnishes new understanding of NP electromigration in complex environments, establishing a robust and predictive model to guide the design and characterization of functionalized NPs.

Observation and Photophysical Characterization of Silicon Phthalocyanine J-Aggregate Dimers in Aqueous Solutions

The use of macrocyclic molecules for both imaging and photodynamic therapy (PDT) has proven to be a powerful method for assessing and treating diseases, respectively. However, many potential candidates for these applications rely on rigid organic structures which are hydrophobic and thus lead to possible aggregation in aqueous solutions such as blood. Here, we describe the discovery of noncovalent J-aggregate dimers of the asymmetrically, axially modified silicon phthalocyanine 4 (Pc 4) in aqueous solutions through steady-state and time-resolved spectroscopy. Remarkably, the monomer-dimer equilibrium is dictated by water content and pH, with free monomers resulting in favorable solvation conditions even after formation of the dimer complex. This work sheds light on previous observations of Pc 4 behavior in cells during PDT, and can further elucidate the structure-activity relationship of these important molecules.

Electron-transfer dependent photocatalytic hydrogen generation over cross-linked CdSe/TiO2 type-II heterostructure

Developing type-II heterostructures with a spatial separation of photoexcited electrons and holes is a useful route to promote photocatalytic hydrogen generation. However, few investigations on the charge transfer process across the heterojunction have been carried out, which can allow us to uncover the reaction mechanism. Herein, CdSe quantum dots (QDs) and TiO2 nanocrystals were synthesized and combined in water yielding CdSe/TiO2 type II heterostructures. It was found that mercaptopropionic acid as bifunctional molecules could bind with CdSe and TiO2 to form a cross-linked morphology. The charge carrier dynamics of bare CdSe and CdSe/TiO2 were detected using femtosecond transient absorption spectroscopy. In the presence of TiO2, the average exciton lifetime of CdSe QDs was apparently decreased, owing to the electron transfer from photoexcited CdSe to TiO2. Particularly, the electron-transfer rate from small CdSe QDs (3.0 nm) was much faster than that from big CdSe QDs (4.2 nm). The improved photocatalytic hydrogen generation was observed for CdSe/TiO2 compared to bare CdSe QDs. The enhancement factor for small CdSe QDs was higher than that for big CdSe QDs, which was in good agreement with the electron-transfer rates. This result indicated that the electron transfer between CdSe and TiO2 played an important role in photocatalytic hydrogen generation on CdSe/TiO2 type-II heterostructure. Our study provides a fundamental guidance to construct efficient heterostructured photocatalysts by delicate control of the band alignment.

Photophysics of silicon phthalocyanines in aqueous media.

Phthalocyanines have been used as photodynamic therapy (PDT) agents because of their uniquely favorable optical properties and high photostability. They have been shown to be highly successful for the treatment of cancer through efficient singlet-oxygen ((1)O(2)) production. However, due to their hydrophobic properties, the considerations of solubility and cellular location have made understanding their photophysics in vitro and in vivo difficult. Indeed, many quantitative assessments of PDT reagents are undertaken in purely organic solvents, presenting challenges for interpreting observations during practical application in vivo. With steady-state and time-resolved laser spectroscopy, we show that for axial ligated silicon phthalocyanines in aqueous media, both the water:lipophile ratio and the pH have drastic effects on their photophysics, and ultimately dictate their functionality as PDT drugs. We suggest that considering the presented photophysics for PDT drugs in aqueous solutions leads to guidelines for a next generation of even more potent PDT agents.